Recent reports by several laboratories indicate that not all non-essential target loci are equally capable of detecting chromosomal mutations. The present study was undertaken to determine if both the tk locus in mouse
lymphoma cells and the
hgprt locus in Chinese hamster ovary (CHO) cells can be used to quantitate chromosomal mutations. Seven known
mutagens for the tk locus were selected. These compounds were evaluated in the mouse
lymphoma assay and in a
suspension adapted CHO assay for their mutagenicity. In addition to the specific locus mutagenesis analysis, mouse
lymphoma and CHO cells were evaluated for the frequency of gross
chromosome aberrations. From these investigations, it appears that only those compounds [2-methoxy-6-chloro-9-(3-[ethyl-2-chloroethyl] aminopropylamino)-
acridine-dihydrochloride (
ICR 170),
ethyl methanesulfonate (EMS) and
methyl methanesulfonate (MMS)] that induce significant numbers of large-colony
thymidine kinase (TK) mutants also induce significant numbers of
hypoxanthine-guanine phosphoribosyltransferase (
HGPRT) mutants. The four
acrylates evaluated (
methyl acrylate,
ethyl acrylate,
trimethylolpropane triacrylate and tetraethyleneglycol diacrylate) induced almost exclusively small-colony TK mutants and very few if any
HGPRT mutants. Aberration analysis revealed that both the mouse
lymphoma and CHO cells responded to the clastogenicity of the compounds (except for
ICR 170 which was not positive in CHO cells) and that neither cell line was clearly more sensitive than the other to the
clastogens tested. It is significant that the four
acrylates give little or no evidence of genotoxicity when evaluated using selection for
HGPRT-deficient mutants, yet are clearly clastogenic to the same cells in the same experiment. These results are consistent with the hypothesis that the
hgprt locus may not be useful as a marker to evaluate the clastogenic component of a genotoxic compound. The present study adds to the increasing number of studies that support the view that the hemizygous nature of the
hgprt locus permits the recovery of mutations primarily affecting the function of a single gene; whereas the heterozygous nature of the tk locus permits the recovery of both single gene and chromosomal mutations.