Mutation frequency decline following chemical mutagenesis of Salmonella typhimurium

The occurrence is reported of a mutation frequency decline process (MFD) following treatment of Salmonella typhimurium strain trpC₃ with two chemical mutagens which give rise predominantly to suppressor revertants. With the carcinogen 4-nitroquinoline-N-oxide (4NQO) the results are analogous to those obtained for UV-mutagenesis. In the case of methoxynamine, the process is due to specific excision of premutational lesions, since lethality is low and lethal lesions are non-excisable. Mutants are described which cannot perform MFD of lesions induced by one or both of the chemical mutagens, indicating that the loss of revertants is in each case due to a bacteial repair system rather than to spontaneous degradation of the induced lesion. The mutants, however, were isolated because of an altered response to UV mutagenesis, viz., their ability to express UV-induced mutants in the absence of amino acids to stimulate active post-irradiation protein synthesis. In all other respects tested, their response to UV is identical with that of the parent strain. The hypothesis is discussed that the total absence of UV-induced revertants of the strain S. typhimurium trpC₃ when active protein synthesis is inhibited is due to two processes, first, rapid MFD due to the specific excision of pyrimidine dimers (the predominant UV-lesion) and secondly, the slow excision of other premutational damage which may be other photoproducts or secondary distortions caused by close juxtaposition of several pyrimidine dimers.