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Interspecies Comparison of Human and Rat Mammary Epithelial Cell-mediated Mutagenesis by Polycyclic Aromatic Hydrocarbons¹

Department of Human Oncology, Environmental Toxicology Center and University of Wisconsin Clinical Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin 53792

In order to compare the interactions of procarcinogens with mammary cells from humans and rats, a uniform set of mediated mutagenesis assays has been established. In these assays, species-specific mammary epithelial cells activate procarcinogens, and specific locus mutations are quantitated in cocultured V-79 cells. Mutations were induced in the rat mammary cell coculture system exposed to 7,12-dimethylbenz(a)anthracene but not benzo(a)pyrene. In contrast, in the human mammary cell coculture system benzo(a)pyrene was much more effective than 7,12-dimethylbenz(a)anthracene in the induction of mutations. These results suggest caution in extrapolating carcinogenesis data between rodents and humans. They also suggest that the relationship between the ubiquitous environmental xenobiotic benzo(a)pyrene and the etiology of human breast cancer requires further exploration.

¹ Supported by Grants CA30295 and CA28954 from the Department of Health and Human Services, NIH, National Cancer Institute.

² Recipient of support from postdoctoral training Grant ES07015 from the National Institute of Environmental Health Services.

Received 12/26/85. Revised 4/ 9/86. Accepted 7/ 9/86.

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