Protection of mice against 7,12-dimethylbenz(a)anthracene-induced skin tumors by immunization with a fluorinated analog of the carcinogen

Abstract

5-Fluoro-12-methylbenzanthryl-7-acetic acid (5-FMBAAA) is an analog of the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) with little or no carcinogenic activity. CD-1 mice immunized with 5-FMBAAA conjugated to bovine serum albumin (BSA) developed serum antibodies capable of binding DMBA. As a means of testing whether this immunization protected against DMBA-induced tumors, a low-dose carcinogenesis model system was developed, entailing the repeated skin application of 25 ng DMBA in dodecane alternating with applications of the tumor promoter, phorbol myristate acetate. Mice immunized with the 5-FMBAAA:BSA conjugate and subsequently exposed to this low-dose regimen for 40 weeks developed significantly fewer skin tumors (0.23 papilloma/mouse) than did unimmunized mice, mice immunized with BSA, or mice immunized with an unconjugated mixture of BSA and 5-FMBAAA (0.47 to 0.54 papilloma/mouse). Immunization did not reduce tumor incidence in mice treated with phorbol myristate acetate alone. The results suggest that, when mice are exposed to a carcinogen at doses low enough to approach environmental levels, immunization against the carcinogen can provide specific protection.