Immunosuppression and Carcinogenesis: Contrasting Effects With 7,12-Dimethylbenz[a]anthracene, Benz[a]pyrene, and 3-Methylcholanthrene

Summary

Neonatal injection of 30 μg of 7,12-dimethylbenz[a]anthracene (DMBA) results in a permanently suppressed humoral antibody response and a high tumor incidence (Ball et al., Science 152: 650–651, 1966). This immunosuppression has been characterized further to show that, after neonatal injection of 60 μg DMBA, both primary and secondary immunological responses to sheep erythrocytes were suppressed. In addition, the primary hemolysin response could be depressed by a dose of DMBA as low as 6 μg given to neonatal mice. This dose resulted in a thymic lymphoma incidence of 20%. The degree to which the humoral antibody response was depressed depended on the dose of DMBA injected. On the other hand, a carcinogenic dose of DMBA given to adult mice resulted in only a 1-day delay in reaching maximum antibody levels; thereafter no difference in the amount of I_gG or I_gM between control and treated mice could be detected. In contrast to the effect of DMBA on newborns, carcinogenic doses of benz[a]pyrene (BaP) and 3-methylcholanthrene (MCA) injected at birth did not result in any detectable immunosuppression. Although immunosuppression by a neonatal injection of DMBA correlates with a high yield of tumors of the lymphatic tissue, such a correlation was not found with BaP and MCA. The possible implications of these results are discussed.