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Jan Alexander - One of the best experts on this subject based on the ideXlab platform.
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Correspondence between flat Aberrant Crypt Foci and mucin-depleted Foci in rodent colon carcinogenesis.
Anticancer research, 2008Co-Authors: Angelo Pietro Femia, Jan Erik Paulsen, Jan Alexander, Piero Dolara, Giovanna CaderniAbstract:Background: Flat Aberrant Crypt Foci (flat ACF) and mucin-depleted Foci (MDF) are preneoplastic lesions identified in the colon of carcinogen-treated rodents stained withmethyleneblue(MB)andhighirondiamine-alcianblue (HID-AB), respectively. The correspondence between flat ACF and MDF in the same colon of Min mice treated with azoxymethane (AOM) and of F344 rats treated with 1,2- dimethylhydrazine (DMH) was explored. Materials and Methods: The position of each flat ACF was recorded on a digitally constructed photographic map of the MB-stained colon.The same colons were then stained with HID-AB and the position of each MDF was compared with that of flat ACF.Results:Thefractionofcoincidentlesions,identifiedas both flatACF and MDF with the two staining methods, was 57%and42%,intheMinmiceandF344rats,respectively. Flat ACF or MDF not coincident with the two staining methodswereeitherundetectableorACFwithoneofthetwo methods. Conclusion: Flat ACF and MDF show considerable, but not total, overlap. Identification of preneoplastic lesions is a key step in the development of reliable biomarkers of cancer in short-term carcinogenesis assays. Aberrant Crypt Foci (ACF), identified in unsectioned colons stained with methylene blue (MB) in azoxymethane (AOM)-treated mice (1) are purportedly preneoplastic lesions well characterized in humans and animals, therefore, they are widely used as biomarkers in colon carcinogenesis (2). However, possibly due to
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Prevalent location of flat dysplastic Aberrant Crypt Foci near lymphoid follicles in the colon of azoxymethane-treated rats.
Anticancer research, 2006Co-Authors: Jan Erik Paulsen, Inger-lise Steffensen, Hege B. Ølstørn, Jan AlexanderAbstract:In the colon of F344 rats treated with 2 x 15 mg/kg body weight of azoxymethane (AOM), the density (number of lesions/cm 2 /rat) of flat Aberrant Crypt Foci (ACF) was 13-fold higher (p
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A fish oil-derived concentrate enriched in eicosapentaenoic and docosahexaenoic acid as ethyl esters inhibits the formation and growth of Aberrant Crypt Foci in rat colon.
Pharmacology & toxicology, 1998Co-Authors: Jan Erik Paulsen, Tone Stamm, Jan AlexanderAbstract:: It was examined whether the fish oil derived n-3 fatty acid concentrate K85 (51.0% of eicosapentaenoic acid, 35.3% of docosahexaenoic acid and 7.7% of other n-3 fatty acids, all as ethyl esters) could inhibit the initial formation of Aberrant Crypt Foci and the later growth of pre-existing Aberrant Crypt Foci in the colon of male F344 rats treated with the carcinogens dimethylhydrazinc or azoxymethane, the proximate metabolite of dimethylhydrazine. Given intragastrically 5 times a week, K85 caused a dose-dependent reduction of the initial (week 0-6) formation of Aberrant Crypt Foci induced by azoxymethane (2 × 15 mg/kg body weight/injection the first two weeks). The number of Aberrant Crypt Foci was reduced by 36% (P < 0.001) with 3.0 g K85/kg body weight/dose, the largest dose tested. The reduction was most pronounced (46%, P = 0.009) among the fastest growing Aberrant Crypt Foci (Foci with 3 or more Aberrant Crypts). When given in a later phase of the carcinogenesis (week 17-23) a similar intragastric treatment with K85 caused a dose-dependent reduction of the growth of pre-existing Aberrant Crypt Foci induced by dimethylhydrazine (3 × 20 mg/kg body weight/injection the first week). The Crypt multiplicity (Aberrant Crypt/focus) was reduced by 22% (P = 0.016) with 2.24 g K85/kg body weight/dose, the largest dose tested. This was sufficient to completely block the growth of the pre-existing Aberrant Crypt Foci in the treatment period. The arrest of Crypt multiplication was further documented by the 63% reduction (P = 0.03) of the large Aberrant Crypt Foci (Foci with 9 or more Aberrant Crypts). The total number of Aberrant Crypt Foci was not affected.
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Dietary polyamines promote the growth of azoxymethane-induced Aberrant Crypt Foci in rat colon.
Carcinogenesis, 1997Co-Authors: Jan Erik Paulsen, Ragnhild Reistad, Knut Arnet Eliassen, Øystein V. Sjaastad, Jan AlexanderAbstract:We have examined whether dietary polyamines influencethe formation and initial growth of azoxymethane (AOM)-induced Aberrant Crypt Foci (ACF) in rat colon. Effects ofa combination of dietary polyamines at three dose levels(putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poorAIN-76A diet were studied in animals in two differentexperimental situations: animals treated with AOM aloneand animals treated with AOM F difluoromethylornithine(DFMO), a specific inhibitor of endogenous polyaminesynthesis. In both experimental situations, dietary polyam-ines enhanced the growth of ACF, expressed as the numberof large ACF (Foci with three or more Aberrant Crypts,ACF o3), whereas the formation of ACF, expressed as thenumber of ACF, was apparently not altered. In animalstreated with AOM alone, maximal growth enhancing effecton ACF was nearly obtained with the median level ofdietary polyamine. In rats fed a low polyamine diet, basicAIN-76A, DFMO reduced the growth of AOM-inducedACF by 83%. This inhibitory effect of DFMO was counter-acted by dietary polyamines in a dose-dependent manner,and it was abolished at the highest level of polyamines. Inconclusion, it was demonstrated that dietary polyaminesare able to enhance the growth of AOM-induced ACF.Further, dietary polyamines reversed the DFMO-causedinhibition of ACF growth, probably by compensating forthe DFMO-reduced endogenous polyamine synthesis.IntroductionQuantification of formation and growth of Aberrant Crypt Foci(ACF*) in the rodent colon has been used as a short-termbioassay to evaluate the role of nutritional components at avery early stage of colon carcinogenesis (1). Several observa-tions have confirmed the putative association between ACFand colon cancer: colon carcinogens induce ACF in rodents(2); ACF are found in resected colonic mucosa of humans athigh risk of colon cancer (3); colon cancer chemopreventiveagents inhibit the induction and growth of ACF (4); some
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Scanning electron microscopy of Aberrant Crypt Foci in rat colon
Carcinogenesis, 1994Co-Authors: Jan Erik Paulsen, Inger-lise Steffensen, Ellen Namork, Jan AlexanderAbstract:The surface of the colon mucosa of 1,2-dimethylhydrazine-treated F344 rats was examined with the scanning electron microscope. A detailed examination of the mucosal topography revealed Foci with one to several Aberrant Crypts. These were seen as structures elevated from the background mucosa. The shape of the luminal openings of the Aberrant Crypts varied from elongated or tortuous to circular. However, we found no ultrastructural variations between the different Aberrant Crypt Foci (ACF) or between the ACF and the background mucosa. There was no direct relationship between the size of ACF and the number of Aberrant Crypts per focus, which may be explained by the mechanism of Crypt fission; in two Aberrant Crypts we discovered the formation of a transverse epithelial septum, dividing the large Crypt into two smaller Crypts. The gross morphology of the ACF observed by scanning electron microscopy and light microscopy was in principle the same.
Daniel W. Rosenberg - One of the best experts on this subject based on the ideXlab platform.
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abstract 3734 modified dietary inflammatory index and increased number of colonic Aberrant Crypt Foci
Cancer Research, 2015Co-Authors: Helen Swede, Daniel W. Rosenberg, Valerie B. Duffy, Masteneh Sharafi, David A Drew, Thomas J Devers, Richard G. StevensAbstract:Pro-inflammatory dietary intake has been linked to the development of colorectal cancer (CRC). There is a paucity of data, however, concerning dietary behavior and prevalence of colonic Aberrant Crypt Foci (ACF), an emerging pre-polyp intermediate endpoint thought to be on the pathway to CRC. We assessed this question in a cross-sectional study of 130 patients (mean age = 57.1 yrs) who received colonoscopy at the Colon Cancer Prevention Program at University of Connecticut Health. Typical diet intake was ascertained from the Brief Block Food Frequency Questionnaire, which provided 29 of the 45 food items in the standard Dietary Inflammatory Index (DII). Using advanced chromoendoscopy imaging, ACF were counted by an endoscopist and external reviewer for consensus. In bivariate analyses between ACF quartiles and mean number of daily servings in four food groups, using the Kruskal-Wallis Non-Parametric test, we found evidence of an inverse dose response with reduced intake of grains (3.9, 3.6, 3.1, 2.7, mean servings per ACF quartile, respectively, p = 0.06) and fruit (1.4, 1.2, 1.0, 1.1, mean servings per ACF quartile, respectively, p = 0.06). We observed little variation in vegetable or dairy intake across ACF quartiles. The association between the modified DII (mod-DII) and ACF number (continuous) was assessed using latent variable modeling controlling for continuous variables of age and waist-hip ratio, and, categorical variables of sex, regular aspirin use (≥ 1 pill per week in past 12 months), regular statin use (≥ 1 pill per week in past 12 months), cigarette smoking (ever, never), polyp history (yes, no) and education level. The final model had a good fit (CFI = 0.92, RMSEA Citation Format: Helen Swede, Masteneh Sharafi, Rong Wu, Valerie B. Duffy, Daniel W. Rosenberg, David A. Drew, Thomas Devers, Richard G. Stevens. Modified dietary inflammatory index and increased number of colonic Aberrant Crypt Foci. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3734. doi:10.1158/1538-7445.AM2015-3734
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Aberrant Crypt Foci as predictors of colorectal neoplasia on repeat colonoscopy
Cancer causes & control : CCC, 2011Co-Authors: Joseph C. Anderson, Bruce M Brenner, Helen Swede, Christopher D. Heinen, Tarun Rustagi, Petr Protiva, Devon C. Pleau, Thiruchandurai V. Rajan, Joel Levine, Daniel W. RosenbergAbstract:Objective To estimate the risk for colorectal neoplasia detected on repeat colonoscopy in relation to Aberrant Crypt Foci (ACF) frequency reported during the previous baseline examination.
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Comment re: "Sporadic Aberrant Crypt Foci are not a surrogate endpoint for colorectal adenoma prevention" and "Aberrant Crypt Foci in the adenoma prevention with celecoxib trial".
Cancer prevention research (Philadelphia Pa.), 2008Co-Authors: Richard G. Stevens, Theresa P. Pretlow, D. Paul Hurlstone, Charles Giardina, Daniel W. RosenbergAbstract:To the Editor: We believe that the enthusiasm of Lance and Hamilton ([1][1]) in embracing the study by Cho et al. ([2][2]) as “seminal” and their finality in dismissing Aberrant Crypt Foci (ACF) as a surrogate end point for chemoprevention trials are misplaced. We are concerned that the
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Epigenetic alterations in RASSF1A in human Aberrant Crypt Foci.
Carcinogenesis, 2006Co-Authors: Emily J. Greenspan, Thiruchandurai V. Rajan, Joel Levine, Melissa A. Jablonski, Glenn S. Belinsky, Daniel W. RosenbergAbstract:CpG island methylation (CIM) is an epigenetic mechanism for transcriptional silencing that occurs at various stages of colon tumorigenesis. CIM has been found in serrated adenomas and hyperplastic polyps. There is also evidence for hypermethylation in Aberrant Crypt Foci (ACF) that are found in resected colons from cancer patients. Our study addresses promoter methylation of a tumor suppressor gene, RASSF1A, within the colonic epithelium of subjects undergoing screening colonoscopies in the absence of synchronous tumors. Patients included in this study were at elevated risk for colorectal cancer (CRC) based on family history, but without a previously occurring or synchronous colon carcinoma. ACF were identified using close-focus magnifying chromendoscopy and collected by biopsy in situ. We isolated ACF and adjacent normal colonic epithelium by laser capture microdissection (LCM) and studied methylation of the RASSF1A promoter region in ACF and in adjacent normal mucosa. Expression of RASSF1A was verified using quantitative real-time polymerase chain reaction (QRT-PCR). We found that 8.6% (3 out of 35) of ACF had K-ras mutations and 24% (6 out of 25) had RASSF1A hypermethylation. Our results demonstrate that RASSF1A hypermethylation and K-ras mutations are not mutually exclusive and are present in patients at elevated risk of CRC. Importantly, CIM of RASSF1A is an early epigenetic aberration, occurring in the absence of synchronous colon tumors and is not accompanied by field effects into the surrounding epithelium.
Mami Takahashi - One of the best experts on this subject based on the ideXlab platform.
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Reduction in formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP)-induced Aberrant Crypt Foci in the rat colon by docosahexaenoic acid (DHA)
2016Co-Authors: Mami Takahashi, Takashi Sugimura, Yukari Totsuka, Kazunori Fukuda, Atsuko Oguri, Keiji WakabayashiAbstract:4To whom correspondence should be addressed Docosahexaenoic acid (DHA), a major component of fish oil, suppresses the formation and growth of Aberrant Crypt Foci induced by 1,2-dimethylhydrazine and azoxymethane. In the present study we examined the effects of intragastric gavage administration of DHA on the yield of rat colonic Aberrant Crypt Foci due to treatment with a heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which induces colon cancer in male F344 rats and is considered to be a possible human colon carcinogen. Male F344 rats were given a standard diet (AIN-76A) and received 10 doses of PhIP (75 mg/kg body wt, by intragastric intubation, on days 1–5 and 8–12) with or without intra-gastric application of 1 ml DHA 4 h prior to each carcinogen treatment, followed by further DHA dosing. The numbers of PhIP-induced Aberrant Crypt Foci per colon after 4 and 12 weeks DHA administration were significantly reduced to 47 and 38 % respectively of the values obtained when PhIP alone was used. The mean number of Aberrant Crypts per focus was also decreased by DHA treatment. At week 4 the PhIP2DNA adduct levels in the colon of rats from the PhIP1DHA group were approximately two thirds of the PhIP group value. The results thus suggest that DHA exerts a preventive effect on PhIP-induced colon carcino-genesis
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Reduction in formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced Aberrant Crypt Foci in the rat colon by docosahexaenoic acid (DHA).
Carcinogenesis, 1997Co-Authors: Mami Takahashi, Kazunaga Yazawa, Takashi Sugimura, Yukari Totsuka, Kazunori Fukuda, Atsuko Oguri, Masuda Mitsuharu, Keiji WakabayashiAbstract:Docosahexaenoic acid (DHA), a major component of fish oil, suppresses the formation and growth of Aberrant Crypt Foci induced by 1,2-dimethylhydrazine and azoxymethane. In the present study we examined the effects of intragastric gavage administration of DHA on the yield of rat colonic Aberrant Crypt Foci due to treatment with a heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which induces colon cancer in male F344 rats and is considered to be a possible human colon carcinogen. Male F344 rats were given a standard diet (AIN-76A) and received 10 doses of PhIP (75 mg/kg body wt, by intragastric intubation, on days 1-5 and 8-12) with or without intragastric application of 1 ml DHA 4 h prior to each carcinogen treatment, followed by further DHA dosing. The numbers of PhIP-induced Aberrant Crypt Foci per colon after 4 and 12 weeks DHA administration were significantly reduced to 47 and 38% respectively of the values obtained when PhIP alone was used. The mean number of Aberrant Crypts per focus was also decreased by DHA treatment. At week 4 the PhIP-DNA adduct levels in the colon of rats from the PhIP+DHA group were approximately two thirds of the PhIP group value. The results thus suggest that DHA exerts a preventive effect on PhIP-induced colon carcinogenesis.
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Reduction in Formation and Growth of 1,2-Dimethylhydrazine-induced Aberrant Crypt Foci in Rat Colon by Docosahexanoic Acid
Cancer research, 1993Co-Authors: Mami Takahashi, Toshinari Minamoto, Naoyuki Yamashita, Kazunaga Yazawa, Takashi Sugimura, Hiroyasu EsumiAbstract:The effect of intragastric gavage administration of docosahexaenoic acid (DHA) on the formation of 1,2-dimethylhydrazine (DMH)-induced Aberrant Crypt Foci in rat colon was investigated. Male F344 rats were treated three times s.c. with 20 mg/kg of DMH and were given either 0.7 ml of DHA or water intragastrically 5 times a week for 4, 8, or 12 weeks from the day before the first carcinogen treatment. The numbers of DMH-induced Aberrant Crypt Foci per colon after 4, 8, and 12 weeks of DHA treatment were approximately 40% of those in the respective control groups, and the differences were statistically significant. The numbers of Foci reached plateau levels at 8 weeks in both the DHA-treated and control groups. The mean number of Aberrant Crypts per focus was also significantly smaller in the group given DHA than that in the control group at each time. These results suggest that DHA suppresses the formation and growth of Aberrant Crypt Foci and has a preventive effect on colon carcinogenesis.
Luca Roncucci - One of the best experts on this subject based on the ideXlab platform.
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Aberrant Crypt Foci in colorectal carcinogenesis cell and Crypt dynamics
Cell Proliferation, 2000Co-Authors: Luca Roncucci, F. Vaccina, Monica Pedroni, Piero Benatti, Marzona And L And, A. De PolAbstract:Aberrant Crypt Foci (ACF) have been identified on the colonic mucosal surface of rodents treated with colon carcinogens and of humans after methylene-blue staining and observation under a light microscope. Several lines of evidence strongly suggest that ACF with certain morphological, histological, cell kinetics, and genetic features are precursor lesions of colon cancer both in rodents and in humans. Thus, ACF represent the earliest step in colorectal carcinogenesis. This paper has the main purpose of reviewing the evidence supporting this view, with particular emphasis on cell and Crypt dynamics in ACF. ACF have been used as intermediate biomarkers of cancer development in animal studies aimed at the identification of colon carcinogens and chemopreventive agents. Recently, evidence has also shown that ACF can be effectively employed in chemopreventive studies also in humans.
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Scanning electron microscopy of Aberrant Crypt Foci in human colorectal mucosa.
Anticancer research, 1998Co-Authors: F. Vaccina, F. Scorcioni, Monica Pedroni, M G Tamassia, M. P. De Leon, A. De Pol, Laura Marzona, Luca RoncucciAbstract:BACKGROUND Aberrant Crypt Foci (ACF) are clusters of morphologically altered Crypts which can be observed by light or stereomicroscopy on the mucosal surface of the colon after staining with methylene-blue. They probably represent one of the earliest events in human colorectal carcinogenesis. The main purpose of the present study was to observe the surface features of Aberrant and normal colonic Crypts in humans using scanning electron microscopy (SEM) in order to find and measure differences between Aberrant and normal. MATERIALS AND METHODS Fifteen mucosal specimens containing ACF and 8 with normal mucosa taken from patients operated on for colon cancer were observed under a scanning electron microscope. RESULTS By SEM ACF were easily observed on the mucosal surface, because they showed a well defined border and were elevated on the mucosal surface. Under higher magnification luminal openings of Aberrant Crypts had a larger overall average diameter than normal (37.6 microns +/- 13.5, mean +/- SD, vs 15.9 microns +/- 4.9, P = 0.001), though when Crypt multiplicity of ACF (number of Crypts per ACF) was higher, the diameter of luminal openings tended to be smaller and similar to those of normal Crypts, with weak negative correlation between Crypt multiplicity of ACF and mean diameter of Aberrant luminal openings (r = 0.27). Finally, the mucosal surface among Aberrant Crypts was flattened because of a loss of microvilli. in conclusion, scanning electron microscopy allows a better definition of the topological features of Aberrant Crypt Foci than light or stereomicroscopy.
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Aberrant Crypt Foci in patients with colorectal cancer
British journal of cancer, 1998Co-Authors: Luca Roncucci, Monica Pedroni, M G Tamassia, Lorena Losi, S Modica, M Ghidoni, R. Fante, C. Di Gregorio, Antonio Manenti, L. GafaAbstract:Aberrant Crypt Foci (ACF) are clusters of abnormally large colonic Crypts identified on the mucosal surface of the human colon. They are thought to be preneoplastic lesions. The aim of the present study was to compare density (number of ACF per square cm of mucosal surface), Crypt multiplicity (number of Crypts per ACF) and histology of ACF in colonic resections of colorectal cancer patients resident in two Italian provinces with a twofold difference in colorectal cancer incidence rates. Thirty-two and 26 colonic resections were collected after operation in Ragusa (Southern Italy) and Modena (Northern Italy), respectively, and fixed in 10% formalin. Mucosal layers were observed under a light microscope at 25x after staining with methylene blue. Density of ACF was significantly higher in Modena (median 0.101 ACF cm(-2)) than in Ragusa (0.049, P = 0.001), whereas there was no difference in Crypt multiplicity. ACF were classified into three groups according to histological features: ACF with mild alterations (hypertrophic ACF, 73%), ACF with hyperplasia (hyperplastic ACF, 17%) and ACF with dysplasia (microadenomas, 10%). The proportions of ACF in the three groups were similar in the two provinces. Density of ACF was higher and Crypt multiplicity lower proceeding from proximal to distal large bowel. Microadenomas were observed only in the colon, whereas hyperplastic ACF were more frequent in the rectum. In conclusion, density of ACF correlates with colorectal cancer rates in two Italian provinces, and shows a positive gradient from proximal to distal large bowel. Histology of ACF suggests that they may be precursors of both hyperplastic and adenomatous polyps. These data provide further evidence of the role of ACF in human colorectal carcinogenesis.
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K-ras and p53 mutations in human colorectal Aberrant Crypt Foci.
The Journal of pathology, 1996Co-Authors: Lorena Losi, Luca Roncucci, Carmela Di Gregorio, Maurizio Ponz De Leon, Jean BenhattarAbstract:Aberrant Crypt Foci (ACF) are putative precursor lesions of colon cancer, recently identified on the methylene blue-stained mucosal surface of human colon. No mutations in K-ras or p53 genes were found by non-radioactive single-strand conformation polymorphism analysis in 14 ACF collected from five patients. Using the more sensitive method of allele-specific polymerase chain reaction (PCR) for K-ras, 8 of 14 ACF were found to contain K-ras mutations, suggesting that mutated cells are present in minute clones in ACF. No dysplasia was observed in any of the ACF containing a mutated clone. The presence of K-ras mutations in ACF suggests that these lesions occur at a very early stage in human colorectal carcinogenesis.
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Classification of Aberrant Crypt Foci and microadenomas in human colon.
Cancer epidemiology biomarkers & prevention : a publication of the American Association for Cancer Research cosponsored by the American Society of Pre, 1991Co-Authors: Luca Roncucci, Alan Medline, W. R. BruceAbstract:Aberrant Crypt Foci (ACF) can be observed and quantified on the mucosal surface of formalin-fixed human colon resections after staining with methylene blue. To determine whether these ACF could be identified in fresh tissue, 10 colon resections were collected after surgery for colorectal cancer. Unfixed and fixed flat normal colonic mucosa from each colon were scored for ACF under a dissecting microscope after methylene blue staining. The number of ACF per cm2 and the average number of Crypts per Foci correlated highly in unfixed and fixed mucosa (r = 0.93 and 0.78, respectively). A significantly higher frequency of lesions was found in left-sided compared to right-sided colon resections. To determine whether the topographic features of the ACF gave an indication of the histological appearance, 68 specimens containing ACF or normal mucosa were examined histologically. The presence of slit-like lumen in the Crypts of ACF on the mucosal surface correlated with the presence of dysplasia at histology, thus identifying microadenomas. These two observations suggest that the topographic classification of ACF in vivo could be used to distinguish microadenomas, a putative precursor lesion of colon cancer.
Keiji Wakabayashi - One of the best experts on this subject based on the ideXlab platform.
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Reduction in formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP)-induced Aberrant Crypt Foci in the rat colon by docosahexaenoic acid (DHA)
2016Co-Authors: Mami Takahashi, Takashi Sugimura, Yukari Totsuka, Kazunori Fukuda, Atsuko Oguri, Keiji WakabayashiAbstract:4To whom correspondence should be addressed Docosahexaenoic acid (DHA), a major component of fish oil, suppresses the formation and growth of Aberrant Crypt Foci induced by 1,2-dimethylhydrazine and azoxymethane. In the present study we examined the effects of intragastric gavage administration of DHA on the yield of rat colonic Aberrant Crypt Foci due to treatment with a heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which induces colon cancer in male F344 rats and is considered to be a possible human colon carcinogen. Male F344 rats were given a standard diet (AIN-76A) and received 10 doses of PhIP (75 mg/kg body wt, by intragastric intubation, on days 1–5 and 8–12) with or without intra-gastric application of 1 ml DHA 4 h prior to each carcinogen treatment, followed by further DHA dosing. The numbers of PhIP-induced Aberrant Crypt Foci per colon after 4 and 12 weeks DHA administration were significantly reduced to 47 and 38 % respectively of the values obtained when PhIP alone was used. The mean number of Aberrant Crypts per focus was also decreased by DHA treatment. At week 4 the PhIP2DNA adduct levels in the colon of rats from the PhIP1DHA group were approximately two thirds of the PhIP group value. The results thus suggest that DHA exerts a preventive effect on PhIP-induced colon carcino-genesis
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Reduction in formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced Aberrant Crypt Foci in the rat colon by docosahexaenoic acid (DHA).
Carcinogenesis, 1997Co-Authors: Mami Takahashi, Kazunaga Yazawa, Takashi Sugimura, Yukari Totsuka, Kazunori Fukuda, Atsuko Oguri, Masuda Mitsuharu, Keiji WakabayashiAbstract:Docosahexaenoic acid (DHA), a major component of fish oil, suppresses the formation and growth of Aberrant Crypt Foci induced by 1,2-dimethylhydrazine and azoxymethane. In the present study we examined the effects of intragastric gavage administration of DHA on the yield of rat colonic Aberrant Crypt Foci due to treatment with a heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which induces colon cancer in male F344 rats and is considered to be a possible human colon carcinogen. Male F344 rats were given a standard diet (AIN-76A) and received 10 doses of PhIP (75 mg/kg body wt, by intragastric intubation, on days 1-5 and 8-12) with or without intragastric application of 1 ml DHA 4 h prior to each carcinogen treatment, followed by further DHA dosing. The numbers of PhIP-induced Aberrant Crypt Foci per colon after 4 and 12 weeks DHA administration were significantly reduced to 47 and 38% respectively of the values obtained when PhIP alone was used. The mean number of Aberrant Crypts per focus was also decreased by DHA treatment. At week 4 the PhIP-DNA adduct levels in the colon of rats from the PhIP+DHA group were approximately two thirds of the PhIP group value. The results thus suggest that DHA exerts a preventive effect on PhIP-induced colon carcinogenesis.
