Susceptibility to the biological effects of polyaromatic hydrocarbons is influenced by genes of the major histocompatibility complex

Polyaromatic hydrocarbons are ubiquitous environmental chemicals that are i mportant mutagens and carcinogens. The purpose of this study was to determi ne whether genes within the major histocompatibility complex (MHC) influenc e their biological activities. Cell-mediated immunity to dimethylbenz(a)ant hracene (DMBA) was investigated in congenic strains of mice. On three diffe rent backgrounds, H-2(k) and H-2(a) haplotype mice developed significantly greater contact-hypersensitivity responses to DMBA than H-2(b), H-2(d), and H-2(s) mice. In B10.A(R1) mice, which are K-k and I-d, a vigorous contact- hypersensitivity response was present, indicating that the response was gov erned by class I, rather than class II, MHC genes. C3H/HeN (H-2(k)) and C3H .SW (H-2(s)) strains were also compared for the development of skin tumors and the persistence of DMBA-DNA adducts. When subjected to a DMBA initiatio n, phorbol 12-tetradecanoate 13-acetate (TPA)-promotion skin-tumorigenesis protocol, C3H/HeN mice, (which develop cell-mediated immunity to DMBA) mere found to have significantly fewer tumors than C3H.SW mice (a strain that f ailed to develop a cell-mediated immune response to DMBA), DMBA-DNA adducts were removed more rapidly in C3H/HeN than in C3H.SW mice. The results indi cate that genes within the MHC play an important role in several of the bio logical activities of carcinogenic polyaromatic hydrocarbons. The observati ons are consistent with the hypothesis that cell-mediated immunity to chemi cal carcinogens serves to protect individuals by removing mutant cells befo re they can evolve into clinically apparent neoplasms.