Effects of a strong and a weak carcinogen on murine alpha/beta interferon production in vivo

A study was designed to determine whether oral doses of carcinogens would reduce an animal's ability to produce interferon. Female BCF1 mice were tested with various doses of benzo[alpha]pyrene (BP) or ethyl methanesulfonate (EMS) po (four to six mice per treatment) and challenged an hour later with the chemical interferon inducer tilorone. After 16-18 hr, mice were sacrificed and bled from the heart. Serum obtained from the blood was assayed for interferon. We found that mice treated with as little as 50 mg/kg BP or EMS had a statistically significant reduction in serum interferon titers compared with control-treated mice. Reductions in interferon titers were also noted at lower doses of the carcinogens, but due to the variability within the small sample size used, the reduction were not statistically significant. On a molar basis, BP was only two to three times more effective at reducing interferon titers than EMS. It was estimated from the data that slightly less than 10 mg/kg BP or 29 mg/kg EMS would be the doses corresponding to 50% reduction in control interferon titers. These doses are well below the reported mutations doses for these chemicals. The effect of carcinogens on in vivo interferon production reported here may be the most sensitive biologic system known for these chemicals.