Inheritance of susceptibility to phototumorigenesis and persistent hyperplasia in F1 hybrids between SENCAR mice and BALB/c or C57BL/6 mice.
SENCAR mice are selectively bred for hypersusceptibility to two-stage chemical skin carcinogenesis. They are also hypersusceptible to UV radiation tumorigenesis with single high-dose, but not chronic low-dose, 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 F1 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 F1 crosses were given a single high dose (8.64 x 10(4) J/m2) of UV radiation (FS40 sunlamps) which causes persistent hyperplasia and tumorigenesis in many SENCAR, but no BALB/c or C57BL/6, mice. F1 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, F1 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 F1 cross, susceptibility to phototumorigenesis decreased in parallel with persistent hyperplasia. These results are consistent with the hypothesis that the two characteristics are mechanistically related.
Strickland
P T
PT
Department of Environmental Health Sciences, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, Maryland 21205.
Swartz
R P
RP
D000818:Animals; D004198:Disease Susceptibility; D051379:Mice; D008807:Mice, Inbred BALB C / Q000235:genetics*; D008810:Mice, Inbred C57BL / Q000235:genetics*; D010787:Photosensitivity Disorders / Q000235:genetics*; D012016:Reference Values; D012878:Skin Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays