Mutagenic activity of some clastogenic chemicals at the hypoxanthine guanine phosphoribosyl transferase locus of Chinese hamster ovary cells

Abstract

4 presumptive clastogens (caffeine, dimethyl sulfoxide, diethylstilbestrol and p,p'-DDE) and 4 chemicals thought to induce chromosomal mutations in L5178Y mouse lymphoma cells (procarbazine X HCl, epichlorohydrin, hycanthone and iodomethane) were tested in the CHO/HGPRT gene mutation assay for the induction of 6-thioguanine-resistant ( 6TGR ) mutants. Of the clastogens, p,p'-DDE was mutagenic at several concentrations and diethylstilbestrol (DES) increased the 6TGR mutant frequency over control levels at the 6.7 and 8.0 micrograms/ml doses, but the results for DES were neither convincing nor significant. Caffeine was not mutagenic although at very high concentrations (6667-8000 micrograms/ml) there was a slight elevation in mutant frequency over background. This was probably due to a selective effect of caffeine against the HGPRT+ phenotype, for 2 different HGPRT- cell lines were refractory to the toxic effects of caffeine at the highest test level (8000 micrograms/ml). All 4 'chromosomal mutagens' produced dose-related increases in mutant frequencies at the HGPRT locus of these CHO cells. 6TGR colonies were generally uniform in size when normal precautions were taken to prevent the formation of satellite (secondary) colonies. Excepting DES, dimethyl sulfoxide, and caffeine, these data demonstrate that 5 of 8 clastogenic chemicals reproducibly induce mutations at the HGPRT locus of CHO cells which lack the small colony-forming potential of 3.7.2C L5178Y cells.