Genotypic differences in host immunoreactivity and their effect on the development of polycyclic hydrocarbon-induced tumors

Abstract

Polyaromatic hydrocarbons are ubiquitous environmental contaminants that are known primarily for their mutagenic and carcinogenic properties. In mice, when applied to the skin, they also act as antigenic substances, capable of initiating a cell-mediated immune response (contact hypersensitivity). Using dimethylbenz(a)anthracene (DMBA) as a prototype, studies from this laboratory have found that genetic polymorphisms, at the Ah receptor locus, the major histocompatibility complex and the Lps locus, control the magnitude of the cell-mediated immune response to these carcinogenic compounds. Strains of mice that metabolize polyaromatic hydrocarbons well and can be immunized to them are less likely to develop cutaneous tumors when subjected to a polyaromatic hydrocarbon-initiation, TPA-promotion cutaneous carcinogenesis protocol. It may thus be possible to assess individual susceptibility to polyaromatic hydrocarbon-induced tumors by characterizing one's ability to metabolize polyaromatic hydrocarbons and his or her immune response to these agents.