Species difference in the ovarian toxicity of 1,3-butadiene epoxides in B6C3F1 mice and Sprague-Dawley rats. 1996

J K Doerr, and E A Hollis, and I G Sipes
Department of Pharmacology and Toxicology, University of Arizona, College of Pharmacy, Tucson 85721, USA.

1,3-Butadiene (BD) is an ovarian carcinogen in mice, but not in rats. Since species variation in metabolism of BD has been associated with the greater sensitivity of mice to BD-induced carcinogenicity, the extent of biotransformation and detoxification of BD and its epoxides may play a critical role in other ovotoxic effects of this compound. Thus, the ovotoxic potency of the BD epoxides was determined. Butadiene monoepoxide (BMO, 0.005-1.43 mmol/kg b.w.), butadiene diepoxide (BDE, 0.002-0.29 mmol/kg b.w.), or vehicle was administered i.p. to female B6C3F1 mice and Sprague-Dawley rats for 30 days. Following day 30, tissues were removed and weighed, and the number of pre-antral ovarian follicles counted. BMO was ovotoxic in mice as demonstrated by decreases in reproductive organ weights (1.43 mmol/kg b.w.) and follicular counts, but not in rats at any dose tested. In mice the ED50 values for BMO for small and growing follicles were 0.29 and 0.40 mmol/kg b.w., respectively. BDE was ovotoxic in both species, however mice were more sensitive to BDE than rats. Ovarian and uterine weights were decreased in mice at 0.14 and 0.29 mmol/kg b.w. of BDE treatment, and in rats at 0.29 mmol/kg b.w. only. The ED50 values for BDE in mice were 0.10 and 0.14 mmol/kg b.w. for small and growing follicles, respectively, ED50 values could not be determined in rats since only 32% of the follicular population was depleted at the highest concentration tested. Thus, BMO and BDE exhibited a greater ovotoxic potential in mice, as compared to rats. In addition, in each species the diepoxide was the most potent ovotoxicant.

UI MeSH Term Description Entries
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D010053 Ovary The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE. Ovaries
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004852 Epoxy Compounds Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS. Epoxide,Epoxides,Epoxy Compound,Oxiranes,Compound, Epoxy,Compounds, Epoxy
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013045 Species Specificity The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species. Species Specificities,Specificities, Species,Specificity, Species
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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