A MAJOR HISTOCOMPATIBILITY COMPLEX-LINKED LOCUS IN THE RAT CRITICALLY INFLUENCES RESISTANCE TO DIETHYLNITROSAMINE CARCINOGENESIS

Major histocompatibility complex (MHC)-linked deletions in the rat are associated with defects in growth and development and increased susceptibility to chemical carcinogens. The present study maps a locus critical for determining susceptibility to diethylnitrosamine (DEN) carcinogenesis by using two groups of MHC-recombinant rats congenic for the MHC and its linked region. Resistance to DEN segregates with a locus (rcc+) that maps between RT1.E and ft, and its homozygous loss markedly increases susceptibility to DEN. Non-MHC genes do not significantly influence the susceptibility of these strains to DEN. The existence of the rcc locus adds support to our hypothesis that some genes in the MHC-linked region play a major role in both normal and abnormal growth.