Benzo(a)pyrene (BaP), a series of its metabolic derivatives, and benzo(e)pyrene, a very weakly carcinogenic isomer, were tested for their biological effects on transformable C3H/10T½ cells. These cells were used as targets in a series of assays designed to measure oncogenic transformation, mutation to ouabain resistance, cytotoxicity, and induction of cytogenetic changes, as evidenced by chromosomal aberrations and sister chromatid exchange. Of all the compounds tested, only the parent hydrocarbon, BaP, and (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene were found to be significantly active in producing transformation and cytogenetic alterations. BaP, (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, and (±)-7α, 8β-dihydroxy-9β, 10β-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, however, were all effective inducers of mutation in C3H/10T½ cells. (±)-7α, 8β-Dihydroxy-9β, 10β-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was the most potent agent in tests for cytotoxicity. Benzo(e)pyrene was inactive in all assays examined. Among the compounds tested, there was a correlation between the ability to induce cytogenetic changes and the ability to produce mutation and transformation. These results support the demonstrated role of (±)-trans-7,8-dihydroxy-7,8,-dihydrobenzo(a)pyrene as a proximal carcinogenic form of BaP and illustrate the utility of the C3H/10T½ cell system as an important tool for the detection of genotoxic damage by carcinogenic chemicals.
This work was supported in part by Grants CA-21036 and CA-11751 from the National Cancer Institute, Grant ES-00002 from the National Institute for Environmental Health Sciences, Contract N01-CP-65831 from the National Cancer Institute, and a grant from the Hoffman LaRoche Foundation.