The effect of diethylstilbestrol as measured by host resistance and tumor susceptibility assays in mice

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Abstract
As part of a program to develop and validate methodology to measure chemically induced immunotoxicity, the effect of DES [diethylstilbestrol] on resistance of adult B6C3F1 female mice to various microorganisms and to challenge with syngeneic tumor cells was evaluated. The mice received s.c. injections of 50 .mu.l corn oil alone or of corn oil containing the equivalent of 0.2, 1 and 4 mg DES/kg d [day] for 14 d. Three days later they were challenged with Listeria monocytogenes, Streptococcus sp., influenza virus, herpes virus, Trichinella spiralis or B16-F10 tumor cells. Host resistance parameters were mortality for the bacterial and viral systems, expulsion of adult parasites from the gut for T. spiralis, and lung weights for the B16-F10 tumor-cell model. Host resistance to L. monocytogenes, herpes virus and T. spiralis was significantly decreased following DES exposure. Resistance to Streptococcus sp. was decreased, but not a statistically significant level following these doses of DES. However, a dose of DES at 8 mg/kg .cntdot. d resulted in a highly significant decrease in resistance to the organism. Resistance to influenza virus was unaffected by the DES. In contrast to the above, host resistance to i.v. administered B16-F10 tumor cells was significantly increased as a consequence of DES exposure. These model systems for measuring alterations in host resistance were indicated to hold potential for the routine screening of drugs, chemicals and environmental agents for their possible immune effects, both adverse and potentiating. The importance of selecting the appropriate assay for evaluating a particular agent was indicated. The necessity for including host resistance assays along with assays to measure specific immune aspects were stressed to assess in the intact animal the overall effect of complex immune interactions following exposure to a test agent.