INTRODUCTION 



plication in the genetics of plants and animals. The small size of bacterial cells 

 ideally suits them for experiments with this agent, and UV is probably the 

 most convenient and widely used mutagenic treatment in microbial experiments. 

 The analysis of UV-effects has been stimulated by the discovery of photore- 

 activation (72, 55). A number of workers have found that a treatment of 

 various types of cells (actinomycete spores, bacteria, bacteriophage, mold 

 spores, Arbacia eggs) with visible light partially cancels both the lethal and 

 the mutation-inducing effects of a previous dose of UV (56, 73, 104, 105, 134). 

 This might suggest that a light-sensitive substance is produced by UV, but the 

 possible nature of this substance and its locus within the cell are obscure. Bac- 

 teriophage inactivated with UV is photoreactivated by visible light only 

 following its absorption into sensitive cells. The effect of UV in inhibiting 

 enzyme synthesis is also subject to photoreactivation (125) but no systems 

 simpler than intact cells have been shown to give such an effect. 



Chemical mutagens. — A byproduct of research on chemical warfare agents 

 during World War II was the realization of the possibility of mutagenic activity 

 of chemicals. The nitrogen and sulfur mustards (jg-chloro-alkylamines and 

 sulfides) have been studied especially extensively, and found to be potent 

 mutagens for all organisms studied. In general, their effects are similar to those 

 of X-rays and UV, but there are differences in details (26). The similarity 

 of effects is made the more pronounced by the fact that mutants that are 

 relatively resistant to "mustard" can be selected in E. coli, strain B, and these 

 mutants also show augmented resistance to UV and X-ray. (33, 138). 



Active programs are under way in several laboratories to screen compounds 

 for mutagenic activity, with bacteria prominent among the test organisms. 

 The methodology of such a program, and some of the precautions needed 

 to justify a positive conclusion, are illustrated in Witkin's paper (11). There 

 is a wealth of further literature on this subject, and it is likely to remain an 

 active field. There is so far no rational basis which can be used to predict 

 the activity of new compounds, and substances as diverse as formaldehyde, 

 acriflavine, urethane, caffeine, hydrogen peroxide, and manganous ion are 

 credibly reported as active in one or another system (26, 49, 58, 65, 47). In 

 general, reagents with a high reactivity for labile organic H groups, e.g., for- 

 maldehyde, organic peroxides, acyl halides and sulfates, ethylene oxide, acetic 

 anhydride, and diazomethane are probably mutagenic (86) but this does 

 not account for the mutagenicity of such chemically inactive compounds as 

 caffeine or urethane. 



Much more careful work is needed in this field, but so far there is no 

 convincing evidence for any appreciable specificity in the mutagenic capacities 

 of any of these chemicals or physical treatments. Each of them induces a wide 

 diversity of mutations (as far as this has been investigated), and in general, 

 the results of, e.g., X-ray treatment, would not be readily distinguishable from 

 that of formaldehyde. On the other hand, it is possible that different gene 

 forms may differ in the frequency with which they will respond to different 



1 



