Tests for the mutagenic action of a number of chemicals on Haemophilus influenzae with special emphasis on hydrazine

Abstract

A number of chemicals have been tested for their ability to produce novobiocin-resistant mutants in Haemophilus influenzae. Of these, hydrazine (HZ) proved unique because it induced a fairly high incidence of mutation without killing significant numbers of cells at concentrations ranging over nearly four orders of magnitude. Moreover, its dose-effect curve increased very slowly initially and reached a relatively low maximum. It is suggested that HZ may be acting as both a mutagen and an anti-mutagen in this system. HZ has sometimes been characterized as primarily an inactivating agent rather than as a mutagen. Obviously, quite the opposite is true for H. influenzae. Moreover, a survey of the literature shows that HZ has been used effectively to produce mutations in phage, bacteria, higher plants and Drosophila. There is reason to suspect that it produces mainly single locus mutations rather than chromosomal aberrations, but the amount of information on this point is still very small. The effectiveness of a mutagen can be markedly affected by the criterion of effectiveness used. If a high incidence of mutation with reasonably high cell survival is the criterion, then mutagens that are relatively nontoxic would probably be considered highly effective. In this case, the maximum mutation rate that can be achieved in practice may be controlled either by toxicity or by maxima like the one found for HZ. If, on the other hand, the important criteria are the concentration and exposure time needed to produce a detectable increase in mutation, then some quite toxic mutagens would be considered quite effective even though the maximum mutation that can be produced in practice is low. The first criterion is the one to use in choosing mutagens for detailed analysis of the mutation process, but the second set of criteria may be more suitable for generalizing to other organisms, for example from microorganisms to man, since toxic effects can be quite different in different cell types.