Histocompatibility gene mutation rates, spontaneous and induced by the chemical mutagen procarbazine

The use of histocompatibility mutations in mice for the development of a mutagenicity test has been proposed by several immunologists. The aim of our work was to find a basis for the establishment of the H-test as a mutagenicity test. We therefore determined the spontaneous mutation rates of H-genes in the two inbred mouse strains C3H and C57Bl. Furthermore, we tried to increase the mutation rate by the well-known chemical mutagen procarbazine. The spontaneous mutation rates of H-genes of both strains were identical at about 1.2 x 10(-3). After long-term mutagen treatment with 100 mg procarbazine/kg per week, the mutant frequency increased to about 7% and decreased again when the total dose had reached more than 9 x 100 mg/kg in C57Bl mice and more than 14 x 100 mg/kg in C3H mice. These results are discussed in comparison with procarbazine experiments with other mutagenicity test systems. The feasibility of the H-test for mutagenicity testing remains to be verified by further experiments with other germ-line mutagens.