The Experts below are selected from a list of 207 Experts worldwide ranked by ideXlab platform
Henry E. Holden - One of the best experts on this subject based on the ideXlab platform.
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Oxymetholone: I. Evaluation in a Comprehensive Battery of Genetic Toxicology and In Vitro Transformation Assays*
2016Co-Authors: Henry E. Holden, Debbie Studwell, B. MajeskaAbstract:Oxymetholone is generally assumed to be a nongenotoxic carcinogen. This assumption is based primarily on the results of an Ames test, existing data in repeat-dose toxicology studies, and the predicted results of a 2-yr National Toxicology Program (NTP) rat carcinogenicity bioassay. To provide a comprehensive assessment of its genotoxicity in a standard battery of mutagenicity assays, Oxymetholone was tested in microbial and mammalian cell gene mutation assays, in an i vitro cytogenetics assay (human lympho-cytes), and in an in vivo micronucleus assay. Oxymetholone was also tested in an in vitro morphologic transformation model using Syrian hamster embryo (SHE) cells. These studies were initiated and completed prior to the disclosure of the results of the NTP bioassay. Oxymetholone was tested at doses up to 5,000 μg/plate in the bacterial plate incorporation assay using 4 Salmonella strains and the WP2 uvrA (pKM101) strain of Escherichia coli. There was no induction of revertants up to the highest dose levels, which were insoluble as well as toxic. In the L5178Y tk+/- mouse lymphoma assay, doses up to 30 μg/ml reduced relative survival to ∼30% with no increase in mutants. Male or female human lymphocytes were exposed in vitro to Oxymetholone for 24 hr without S9 or 3 hr with S9 and evaluated for the induction of chromosomal aberrations. There was no increase in aberration frequency over control levels and no difference between male and female cells. Peripheral blood from Tg.AC transgenic mice treated dermally for 20 wk with 0, 1.2, 6.0, or 12.0 mg/day of Oxymetholone and from p53 transgenic mice treated orally by gavage for 26 wk with 125, 625, or 1,250 mg/kg/day of Oxymetholone was evaluated for micronuclei in polychromatic and normochromatic erythrocytes. There wa
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Oxymetholone iii evaluation in the p53 transgenic mouse model
Toxicologic Pathology, 1999Co-Authors: Raymond E. Stoll, Henry E. Holden, Curt H. Barthel, Kerry T. BlanchardAbstract:Oxymetholone has been identified as a suspected nongenotoxic carcinogen and has recently completed testing in a conventional National Toxicology Program (NTP) 2-yr rodent bioassay program. As a syn...
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Oxymetholone: III. Evaluation in the p53+/- Transgenic Mouse Model
Toxicologic pathology, 1999Co-Authors: Raymond E. Stoll, Henry E. Holden, Curt H. Barthel, Kerry T. BlanchardAbstract:Oxymetholone has been identified as a suspected nongenotoxic carcinogen and has recently completed testing in a conventional National Toxicology Program (NTP) 2-yr rodent bioassay program. As a synthetic androgen with a limited historical database in toxicology, Oxymetholone is an ideal candidate for prospective examination of the performance of short-term transgenic mouse models in the detection of carcinogenic activity. In the present series of 3 articles, studies are described where Oxymetholone was evaluated prior to disclosure of the results of the NTP 2-yr bioassay. The accompanying articles provide evidence showing that Oxymetholone is devoid of mutagenic activity yet elicits a positive carcinogenic response in the Tg.AC transgenic mouse model. In the present study, Oxymetholone was administered by oral gavage to p53 heterozygous male and female mice for 26 wk at doses of 125, 625, and 1,250 mg/kg/day. The vehicle was 0.5% aqueous methylcellulose. Positive controls consisted of mice treated daily by oral gavage with 200 or 400 mg/kg/day of p-cresidine in corn oil. The Oxymetholone-treated females showed significantly increased body weight gain and clitoral enlargement attributable to drug treatment. In addition, significant alterations in kidney, liver, and testis weights were attributable to Oxymetholone. However, there were no neoplastic lesions that were attributable to Oxymetholone in either sex. p-Cresidine produced unequivocal bladder neoplasms in both sexes at the high dose and in males at the lower dose. The absence of a neoplastic response with Oxymetholone is consistent with the selectivity of the p53-/- mouse model for detecting carcinogens that act by genotoxic mechanisms.
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Oxymetholone: I. Evaluation in a comprehensive battery of genetic toxicology and in vitro transformation assays.
Toxicologic pathology, 1999Co-Authors: Henry E. Holden, Debbie Studwell, Jenness B. MajeskaAbstract:Oxymetholone is generally assumed to be a nongenotoxic carcinogen. This assumption is based primarily on the results of an Ames test, existing data in repeat-dose toxicology studies, and the predicted results of a 2-yr National Toxicology Program (NTP) rat carcinogenicity bioassay. To provide a comprehensive assessment of its genotoxicity in a standard battery of mutagenicity assays, Oxymetholone was tested in microbial and mammalian cell gene mutation assays, in an in vitro cytogenetics assay (human lymphocytes), and in an in vivo micronucleus assay. Oxymetholone was also tested in an in vitro morphologic transformation model using Syrian hamster embryo (SHE) cells. These studies were initiated and completed prior to the disclosure of the results of the NTP bioassay. Oxymetholone was tested at doses up to 5,000 microg/plate in the bacterial plate incorporation assay using 4 Salmonella strains and the WP2 uvrA (pKM101) strain of Escherichia coil. There was no induction of revertants up to the highest dose levels, which were insoluble as well as toxic. In the L5178Y tk+/- mouse lymphoma assay, doses up to 30 microg/ml reduced relative survival to approximately 30% with no increase in mutants. Male or female human lymphocytes were exposed in vitro to Oxymetholone for 24 hr without S9 or 3 hr with S9 and evaluated for the induction of chromosomal aberrations. There was no increase in aberration frequency over control levels and no difference between male and female cells. Peripheral blood from Tg.AC transgenic mice treated dermally for 20 wk with 0, 1.2, 6.0, or 12.0 mg/day of Oxymetholone and from p53 transgenic mice treated orally by gavage for 26 wk with 125, 625, or 1,250 mg/kg/day of Oxymetholone was evaluated for micronuclei in polychromatic and normochromatic erythrocytes. There was no difference in micronuclei frequency between control and treated animals. These results confirm that Oxymetholone is not genotoxic in a comprehensive battery of mutagenicity assays. In the SHE assay, Oxymetholone produced a significant increase in morphologically transformed colonies at dose levels of 13-18 microg/ml. The lack of genotoxicity of Oxymetholone, the positive response in the in vitro transformation assay, and the results of transgenic mouse carcinogenicity assays will provide an interesting perspective on the results of an on-going NTP rat carcinogenicity bioassay.
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Oxymetholone: II. Evaluation in the Tg-AC transgenic mouse model for detection of carcinogens.
Toxicologic pathology, 1999Co-Authors: Henry E. Holden, Raymond E. Stoll, Kerry T. BlanchardAbstract:Several rodent models are under examination as possible alternatives to the classical 2-yr carcinogenicity bioassay. The Tg.AC transgenic mouse has been proposed as a shorter term model offering the possibility of detecting nongenotoxic and genotoxic carcinogenic agents. Retrospective studies of chemicals with established carcinogenic potential have revealed a close correlation between classical bioassay results and the production of skin tumors in the Tg.AC mouse model. Oxymetholone is a synthetic testosterone derivative that is a suspected carcinogen but has shown no evidence of genotoxic activity in a comprehensive battery of genetic toxicity assays. It currently is being tested by the National Toxicology Program (NTP) in a 2-yr rat carcinogenicity bioassay. Because of its nongenotoxicity and the ongoing chronic bioassay, Oxymetholone was considered an ideal candidate for a prospective evaluation of the predictive validity of the Tg.AC dermal carcinogenicity model. Consequently, a 6-mo dermal study wit...
Kerry T. Blanchard - One of the best experts on this subject based on the ideXlab platform.
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Oxymetholone iii evaluation in the p53 transgenic mouse model
Toxicologic Pathology, 1999Co-Authors: Raymond E. Stoll, Henry E. Holden, Curt H. Barthel, Kerry T. BlanchardAbstract:Oxymetholone has been identified as a suspected nongenotoxic carcinogen and has recently completed testing in a conventional National Toxicology Program (NTP) 2-yr rodent bioassay program. As a syn...
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Oxymetholone: III. Evaluation in the p53+/- Transgenic Mouse Model
Toxicologic pathology, 1999Co-Authors: Raymond E. Stoll, Henry E. Holden, Curt H. Barthel, Kerry T. BlanchardAbstract:Oxymetholone has been identified as a suspected nongenotoxic carcinogen and has recently completed testing in a conventional National Toxicology Program (NTP) 2-yr rodent bioassay program. As a synthetic androgen with a limited historical database in toxicology, Oxymetholone is an ideal candidate for prospective examination of the performance of short-term transgenic mouse models in the detection of carcinogenic activity. In the present series of 3 articles, studies are described where Oxymetholone was evaluated prior to disclosure of the results of the NTP 2-yr bioassay. The accompanying articles provide evidence showing that Oxymetholone is devoid of mutagenic activity yet elicits a positive carcinogenic response in the Tg.AC transgenic mouse model. In the present study, Oxymetholone was administered by oral gavage to p53 heterozygous male and female mice for 26 wk at doses of 125, 625, and 1,250 mg/kg/day. The vehicle was 0.5% aqueous methylcellulose. Positive controls consisted of mice treated daily by oral gavage with 200 or 400 mg/kg/day of p-cresidine in corn oil. The Oxymetholone-treated females showed significantly increased body weight gain and clitoral enlargement attributable to drug treatment. In addition, significant alterations in kidney, liver, and testis weights were attributable to Oxymetholone. However, there were no neoplastic lesions that were attributable to Oxymetholone in either sex. p-Cresidine produced unequivocal bladder neoplasms in both sexes at the high dose and in males at the lower dose. The absence of a neoplastic response with Oxymetholone is consistent with the selectivity of the p53-/- mouse model for detecting carcinogens that act by genotoxic mechanisms.
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Oxymetholone: II. Evaluation in the Tg-AC transgenic mouse model for detection of carcinogens.
Toxicologic pathology, 1999Co-Authors: Henry E. Holden, Raymond E. Stoll, Kerry T. BlanchardAbstract:Several rodent models are under examination as possible alternatives to the classical 2-yr carcinogenicity bioassay. The Tg.AC transgenic mouse has been proposed as a shorter term model offering the possibility of detecting nongenotoxic and genotoxic carcinogenic agents. Retrospective studies of chemicals with established carcinogenic potential have revealed a close correlation between classical bioassay results and the production of skin tumors in the Tg.AC mouse model. Oxymetholone is a synthetic testosterone derivative that is a suspected carcinogen but has shown no evidence of genotoxic activity in a comprehensive battery of genetic toxicity assays. It currently is being tested by the National Toxicology Program (NTP) in a 2-yr rat carcinogenicity bioassay. Because of its nongenotoxicity and the ongoing chronic bioassay, Oxymetholone was considered an ideal candidate for a prospective evaluation of the predictive validity of the Tg.AC dermal carcinogenicity model. Consequently, a 6-mo dermal study wit...
Raymond E. Stoll - One of the best experts on this subject based on the ideXlab platform.
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Oxymetholone iii evaluation in the p53 transgenic mouse model
Toxicologic Pathology, 1999Co-Authors: Raymond E. Stoll, Henry E. Holden, Curt H. Barthel, Kerry T. BlanchardAbstract:Oxymetholone has been identified as a suspected nongenotoxic carcinogen and has recently completed testing in a conventional National Toxicology Program (NTP) 2-yr rodent bioassay program. As a syn...
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Oxymetholone: III. Evaluation in the p53+/- Transgenic Mouse Model
Toxicologic pathology, 1999Co-Authors: Raymond E. Stoll, Henry E. Holden, Curt H. Barthel, Kerry T. BlanchardAbstract:Oxymetholone has been identified as a suspected nongenotoxic carcinogen and has recently completed testing in a conventional National Toxicology Program (NTP) 2-yr rodent bioassay program. As a synthetic androgen with a limited historical database in toxicology, Oxymetholone is an ideal candidate for prospective examination of the performance of short-term transgenic mouse models in the detection of carcinogenic activity. In the present series of 3 articles, studies are described where Oxymetholone was evaluated prior to disclosure of the results of the NTP 2-yr bioassay. The accompanying articles provide evidence showing that Oxymetholone is devoid of mutagenic activity yet elicits a positive carcinogenic response in the Tg.AC transgenic mouse model. In the present study, Oxymetholone was administered by oral gavage to p53 heterozygous male and female mice for 26 wk at doses of 125, 625, and 1,250 mg/kg/day. The vehicle was 0.5% aqueous methylcellulose. Positive controls consisted of mice treated daily by oral gavage with 200 or 400 mg/kg/day of p-cresidine in corn oil. The Oxymetholone-treated females showed significantly increased body weight gain and clitoral enlargement attributable to drug treatment. In addition, significant alterations in kidney, liver, and testis weights were attributable to Oxymetholone. However, there were no neoplastic lesions that were attributable to Oxymetholone in either sex. p-Cresidine produced unequivocal bladder neoplasms in both sexes at the high dose and in males at the lower dose. The absence of a neoplastic response with Oxymetholone is consistent with the selectivity of the p53-/- mouse model for detecting carcinogens that act by genotoxic mechanisms.
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Oxymetholone: II. Evaluation in the Tg-AC transgenic mouse model for detection of carcinogens.
Toxicologic pathology, 1999Co-Authors: Henry E. Holden, Raymond E. Stoll, Kerry T. BlanchardAbstract:Several rodent models are under examination as possible alternatives to the classical 2-yr carcinogenicity bioassay. The Tg.AC transgenic mouse has been proposed as a shorter term model offering the possibility of detecting nongenotoxic and genotoxic carcinogenic agents. Retrospective studies of chemicals with established carcinogenic potential have revealed a close correlation between classical bioassay results and the production of skin tumors in the Tg.AC mouse model. Oxymetholone is a synthetic testosterone derivative that is a suspected carcinogen but has shown no evidence of genotoxic activity in a comprehensive battery of genetic toxicity assays. It currently is being tested by the National Toxicology Program (NTP) in a 2-yr rat carcinogenicity bioassay. Because of its nongenotoxicity and the ongoing chronic bioassay, Oxymetholone was considered an ideal candidate for a prospective evaluation of the predictive validity of the Tg.AC dermal carcinogenicity model. Consequently, a 6-mo dermal study wit...
Ann S Clark - One of the best experts on this subject based on the ideXlab platform.
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stanozolol Oxymetholone and testosterone cypionate effects on the rat estrous cycle
Physiology & Behavior, 1998Co-Authors: Ann S Clark, Meg E Blasberg, Erica M BrandlingbennettAbstract:Abstract Clark, A. S., M. E. Blasberg and E. M. Brandling-Bennett. Stanozolol, Oxymetholone, and testosterone cypionate effects on the rat estrous cycle. PHYSIOL BEHAV 63(2) 287–295, 1998.—Anabolic-androgenic steroid (AAS) effects on the estrous cycle of adult Long-Evans rats were examined in four different experiments. Sexual receptivity, vaginal cytology, and body weight were monitored throughout two-week baseline, AAS treatment, and recovery periods. In Experiments 1–3, rats were administered stanozolol, Oxymetholone, or testosterone cypionate within dose ranges selected to mimic the human abuse levels of each compound. In these studies, the highest doses of stanozolol (5 mg/kg), Oxymetholone (12 mg/kg), or testosterone cypionate (7.5 mg/kg) disrupted the cyclical display of sexual receptivity and vaginal estrus. To compare effects on estrous cyclicity across AAS compounds, rats in Experiment 4 received a single dose (7.5 mg/kg) of each compound for 2 weeks. At the 7.5 mg/kg dose, all AAS compounds interfered with the cyclical display of vaginal estrus, although effects on sexual receptivity were not uniform. No striking AAS effects on body weight were seen in any experiment. The short-term administration of AAS compounds at high doses disrupts female neuroendocrine function in rats.
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comparison of the effects of stanozolol Oxymetholone and testosterone cypionate on the sexual behavior of castrated male rats
Behavioral Neuroscience, 1997Co-Authors: Ann S Clark, Elizabeth V HarroldAbstract:In 3 experiments, adult male Long-Evans rats were castrated and treated daily with an anabolic-androgenic steroid (AAS) compound (either stanozolol, Oxymetholone, or testosterone cypionate) for 6 weeks. Subjects were assigned to 5 groups that received injections of a high, medium, or low dose of the AAS, testosterone propionate, or the oil vehicle. Stanozolol failed to maintain ejaculation at any dose tested. Although some subjects receiving the low dose of Oxymetholone ejaculated, Oxymetholone generally failed to stimulate ejaculation above the levels of the oil group. Testosterone cypionate sustained ejaculation at all doses tested. The relative potency of the medium dose of each AAS in the sex accessory tissues was (from most potent to least potent): testosterone cypionate > stanozolol = Oxymetholone = oil. Thus, these 3 AAS compounds produced a range of behavioral and endocrine responses in castrated male rats.
Elizabeth V Harrold - One of the best experts on this subject based on the ideXlab platform.
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comparison of the effects of stanozolol Oxymetholone and testosterone cypionate on the sexual behavior of castrated male rats
Behavioral Neuroscience, 1997Co-Authors: Ann S Clark, Elizabeth V HarroldAbstract:In 3 experiments, adult male Long-Evans rats were castrated and treated daily with an anabolic-androgenic steroid (AAS) compound (either stanozolol, Oxymetholone, or testosterone cypionate) for 6 weeks. Subjects were assigned to 5 groups that received injections of a high, medium, or low dose of the AAS, testosterone propionate, or the oil vehicle. Stanozolol failed to maintain ejaculation at any dose tested. Although some subjects receiving the low dose of Oxymetholone ejaculated, Oxymetholone generally failed to stimulate ejaculation above the levels of the oil group. Testosterone cypionate sustained ejaculation at all doses tested. The relative potency of the medium dose of each AAS in the sex accessory tissues was (from most potent to least potent): testosterone cypionate > stanozolol = Oxymetholone = oil. Thus, these 3 AAS compounds produced a range of behavioral and endocrine responses in castrated male rats.
