Induction of micronuclei and cell cycle arrest by some tri‐ and tetrachlorobiphenyls in mammalian cells deficient in xenobiotic‐metabolizing enzymes

Polychlorinated biphenyls (PCBs) are persistent organic pollutants with continued public health concerns. The lower chlorinated biphenyls are supposed to be mutagenic following metabolic activation. However, in a preliminary study, we recently observed induction of micronuclei by several PCBs in a subclone of Chinese hamster V79 cell line, V79‐Mz, which is deficient in xenobiotic‐metabolizing enzyme activities. In this study, metabolism‐free genotoxicity of PCBs was investigated, using 10 tri‐ and tetrachlorobiphenyls, in V79, V79‐Mz, and human hepatoma (HepG2) cell lines. Among the four tetrachlorobiphenyls, 2,4,4′,5‐ and 2,3′4,4′‐tetrachlorobiphenyl—both having a noncoplanar configuration—induced micronuclei in V79‐Mz cells, while their coplanar analogs 3,4,4′,5‐ and 3,3′,4,4′‐tetrachlorobiphenyl were inactive. Furthermore, 2,3,3′‐ (PCB 20) and 2,3,4′‐trichlorobiphenyl (PCB 22) started to induce micronuclei in V79‐Mz cells at 10 μM and higher concentrations, demonstrating more potent effects than observed with 2,2′,3‐, 2,2′,4‐, 2,2′,5, and 2,4,4′‐trichlorobiphenyl. As representative compounds, PCB 20 and 22 induced micronuclei in relatively high concentrations in HepG2 cells (p53‐proficient), though they did not induce Hprt gene mutations in V79‐Mz cells. PCB 20 and 22 increased mitotic index and induced cell cycle arrest at the G2/M phase, with effects more potent in V79‐Mz than in V79 cells. This study suggests that 2,3,4′‐ and 2,3,3′‐substituted PCBs are micronuclei inducers and G2/M arresters among a number of trichlorobiphenyls in mammalian cell lines, though with potency lower than that observed recently in V79‐derived cells expressing human CYP2E1. Similarly, some noncoplanar tetrachlorobiphenyls possess metabolism‐independent chromosome‐damaging potentials. Environ. Mol. Mutagen. 58:199–208, 2017. © 2017 Wiley Periodicals, Inc.