MUTAGENIC RESPONSES OF L5178Y MOUSE CELLS AT THE TK AND HPRT LOCI

The expression of multiple recessive genes by aberrant mitotic lesions plays a major part in carcinogenesis. These lesions include intrageni c mutations as well as chromosomal lesions. An in vitro model for stud ying carcinogenesis should respond to all these lesions. Mutagenesis s tudies that target hemizygous loci may not be useful in studying chrom osomal mechanisms because lesions incorporating essential genes alread y missing on the inactive, homologous chromosome may be lethal to the cell. Cells heterozygous at the selectable gene may survive. Using L51 78Y mouse cells, we compared the mutagenic responses at the heterozygo us rk and hemizygous hprt loci to four chemicals-benzidine dihydrochlo ride, diglycidylresorcinol ether, nitrofen and p-benzoquinone dioxime. None of the compounds induced clear positive responses at the hprt lo cus. In contrast, all the compounds induced clear or marginal mutageni c responses at the tk locus. These data are consistent with the expect ation that heterozygous loci can detect lesions that are refractory to hemizygous loci. Published by Elsevier Science Ltd.