Inheritance of Susceptibility to Phototumorigenesis and Persistent Hyperplasia in F, Hybrids between SENCAR Mice and BALB/c or C57BL/6 Mice1

SENCAR mice are selectively bred for hypersusceptibility to twostage chemical skin carcinogenesis. They are also hypersusceptible to UV radiation tumorigenesis with single high-dose, but not chronic lowdose, exposures. In addition, SENCAR mice exhibit an exaggerated and persistent epidermal hyperplasia (due to sustained proliferation of the basal cells) in response to UV-induced tissue damage. In the present study, we have examined the inheritance of susceptibility to both phototumorigenesis and persistent hyperplasia in the l;, offspring of SENCAR mice crossed with either of two inbred strains (BALB/c or C57BL/6) which are relatively resistant to phototumorigenesis. A total of 428 mice from the parental strains and reciprocal I-, crosses were given a single high dose (8.64 x IO4 .l/iir) of UV radiation (FS40 sunlamps) which causes persistent hyperplasia and tumorigenesis in many SENCAR, but no BALB/c or C57BL/6, mice. F, hybrids between SENCAR and C57BL/6 mice did not develop persistent hyperplasia or skin tumors, which indicates that susceptibility to both traits is completely recessive to the C57BL/6 genotype. In contrast, F, hybrids between SENCAR and BALB/c mice developed both persistent hyperplasia and skin tumors, although at a much lower incidence than the SENCAR mice, indicating that susceptibility to both traits is only partially (incompletely) recessive to the BALB/c genotype. Thus, in either I , cross, susceptibility to phototumorigenesis decreased in parallel with persistent hyperplasia. These results are consistent with the hypothesis that the two character istics are mechanistically related.