Relationships between Benzo(a)pyrene-DNA Adduct Levels and Genotoxic Effects in Mammalian Cells

摘要

A modification of the doubling dose concept taken from studies in radiation biology was applied to DNA-adduct and genetic toxicology data. The modification, the doubling adduct level, is defined as the number of DNA adducts per unit of DNA required to double the induced frequency of genotoxic response. The data was obtained from concurrent studies, measuring benzo(a)pyrene (B(a)P) induced genotoxic effects and DNA adducts in several short-term bioassay systems: cytotoxicity, gene mutation, and sister-chromatid-exchange (SCE) in Chinese hamster V79 cells; cytotoxicity, gene mutation, and chromosome aberrations in mouse lymphoma L5178Y TK+/- cells; cytotoxicity and enhanced virus transformation in Syrian hamster embryo cells; and cytotoxicity and morphological transformation in C3H10T1/2CL8 mouse embryo fibroblasts. Both total B(a)P-DNA binding and specific B(a)P-DNA adducts were measured. N2(10beta(7beta, 8alpha,9alpha-trihydroxy-7,8,9,10-tetra- hydrobenzo(a)pyrene)ly)deoxyguanosine (BPDE I-dG) was one of the major adducts identified in all bioassay systems.