GENOTYPIC DIFFERENCES IN HOST IMMUNOREACTIVITY AND THEIR EFFECT ON THE DEVELOPMENT OF POLYCYCLIC HYDROCARBON-INDUCED TUMORS

Polyaromatic hydrocarbons are ubiquitous environmental contaminants th at are known primarily for their mutagenic and carcinogenic properties . In mice, when applied to the skin, they also act as antigenic substa nces, capable of initiating a cell-mediated immune response (contact h ypersensitivity). Using dimethylbenz(a)anthracene (DMBA) as a prototyp e, studies from this laboratory have found that genetic polymorphisms, at the Ah receptor locus, the major histocompatibility complex and th e Lps locus, control the magnitude of the cell-mediated immune respons e to these carcinogenic compounds. Strains of mice that metabolize pol yaromatic hydrocarbons well and can be immunized to them are less like ly to develop cutaneous tumors when subjected to a polyaromatic hydroc arbon-initiation, TPA-promotion cutaneous carcinogenesis protocol. It may thus be possible to assess individual susceptibility to polyaromat ic hydrocarbon-induced tumors by characterizing one's ability to metab olize polyaromatic hydrocarbons and his or her immune response to thes e agents. (C) 1997 Elsevier Science B.V.