Genetics of Susceptibility of Mice to Inhibition of Interferon Induction by Benzo-(a)-pyrene

Abstract

Embryonic fibroblasts were prepared from four different strains of mice: DBA/2, noninducible at the Ah locus for aryl hydrocarbon hydroxylase for carcinogen activation and, therefore, relatively resistant to tumor induction; C57BL/6, normal at the Ah locus; SENCAR, mice innately highly sensitive to tumor induction; and ICR, normal controls for SENCAR mice. The fibroblasts were exposed to the carcinogen benzo-(a)-pyrene at varying dosages. Alpha/beta IFN was next induced with poly(I)(C). Interferon production by cells from C57BL/6 mice was severely inhibited. Interferon production by DBA/2 cells was equally susceptible to inhibition by BP as IFN production by C57BL/6 cells, perhaps because of alternative pathways of activation of BP. Interferon production by SEN-CAR mouse cells was, on the other hand, much more susceptible to inhibition by BP than was IFN production by ICR mouse cells. These results suggest parallels between genetically controlled sensitivity to tumor induction by BP and genetically controlled susceptibility to inhibition of IFN induction by BP.