Polyaromatic
hydrocarbons are ubiquitous
environmental pollutants that are potent
mutagens and
carcinogens. Researchers have taken advantage of these properties to investigate the mechanisms by which chemicals cause
cancer of the skin and other organs. When applied to the skin of mice, several carcinogenic polyaromatic
hydrocarbons have also been shown to interact with the immune system, stimulating immune responses and resulting in the development of
antigen-specific T-cell-mediated immunity. Development of cell-mediated immunity is strain-specific and is governed by
Ah receptor genes and by genes located within the major histocompatibility complex. CD8+ T cells are effector cells in the response, whereas CD4+ T cells down-regulate immunity. Development of an immune response appears to have a protective effect since strains of mice that develop a cell-mediated immune response to carcinogenic polyaromatic
hydrocarbons are less likely to develop
tumors when subjected to a polyaromatic
hydrocarbon skin
carcinogenesis protocol than mice that fail to develop an immune response. With respect to innate immunity, TLR4-deficient C3H/HeJ mice are more susceptible to polyaromatic
hydrogen skin
tumorigenesis than C3H/HeN mice in which TLR4 is normal. These findings support the hypothesis that immune responses, through their interactions with chemical
carcinogens, play an active role in the prevention of chemical skin
carcinogenesis during the earliest stages. Efforts to augment immune responses to the chemicals that cause
tumors may be a productive approach to the prevention of
tumors caused by these agents.