The potential mutagenicity and carcinogenicity of commercial
PCBs has been investigated in both in vivo and in vitro systems and several conclusions can be drawn from these studies. (1)
PCBs can covalently
adduct DNA both in vivo and in vitro (using a source of metabolic activation); the more highly chlorinated biphenyls are poorly metabolized and these compounds tend to exhibit very low binding to
DNA. Based on the structure-activity relationships for
PCBs (Safe, 1984) it is unlikely that the more toxic compounds such as 3,3',4,4',5-penta- and
3,3',4,4',5,5'-hexachlorobiphenyl, would form covalent adducts with
DNA. (2) PCB mixtures and individual compounds exhibit minimal mutagenic activity in most assay systems. (3) The more highly chlorinated PCB mixtures (i.e. greater than 50% Cl by weight) are hepatocarcinogens in rodents whereas data from a limited number of studies suggest that the lower chlorinated mixtures are not carcinogenic. (4) In some model systems, the higher chlorinated PCB mixtures act as promoters of preneoplastic lesions and
hepatocellular carcinomas in rodents treated with a variety of initiators. (5)
Aroclor 1254 acts as a promoter of skin
papilloma formation in HRS/J hairless mice and structure-activity and genetic studies suggest that the
Ah receptor is necessary but not sufficient for the activity of halogenated aryl
hydrocarbons as promoters in hairless mice. (6) Individual PCB congeners and higher chlorinated commercial mixtures also exhibit anti-carcinogenic activity in the CD-1 mouse
skin cancer model. (7) Results from occupational studies suggest that individuals exposed to
PCBs may have an excess of
cancer at some sites, however, the most comprehensive study (Brown, 1987) suggests that there are no significant increases in the overall
cancer rate in workers exposed to
PCBs. Follow-up and continuing epidemiological studies on the PCB-exposed workers are required to further clarify the potential carcinogenic effects of
PCBs on humans. In several strains of rats and mice, there is a high incidence of hepatic preneoplastic lesions and
carcinomas and these lesions can be induced by diverse promoting agents (Schulte-Hermann et al., 1983; Weinstein, 1984). Since
PCBs are not mutagenic and do not readily form covalent adducts with cellular
DNA, it is likely that the higher chlorinated biphenyls are not genotoxic and act as promoters of
carcinogenesis in rodents. A comparable mechanism has been suggested for 2,3,7,8-TCDD (Shu et al., 1987; Weinstein, 1984). For
PCBs, the role of the
Ah receptor in mediating their activity as promoters has not been delineated.(ABSTRACT TRUNCATED AT 400 WORDS)