196 MUTATIONS 



There was an interesting report in 1946 (57) that is worth mention- 

 ing. It was done by a pharmacologist who was interested in toxic 

 effects of nicotine. He gave rats large amounts of nicotine in order to 

 examine any direct effect on fertility. A large number of pairs of rats 

 were used and the number of litters and the litter size were measured. 

 Nicotine did, indeed, lower fertility in these rats. But the interesting 

 thing was that he also kept the progeny and set them up in mating 

 pairs. He found that in the progeny of parents who had been exposed 

 to nicotine there was a statistically significant reduction in litter 

 number and litter size even though these animals had not been exposed 

 to nicotine during their own adult lives. Unfortunately, since the in- 

 vestigators were not looking for genetic effects in the first place, they 

 failed to take certain precautions, for example, against the absorption 

 of nicotine from milk during the weaning period. Moreover, the Fi 

 animals were certainly exposed in utero. 



Spuhler: But there would be an independent effect on fertility? 



Goldstein: There was an effect of treatment. There were adequate 

 control groups of nicotine-treated parents and nonnicotine-treated 

 parents, and nicotine-treated and nonnicotine-treated offspring. I 

 think the design was adequate. 



Auerbach: But they had not treated males and mated them to 

 untreated females? 



Goldstein: No, that's right. That would have been interesting to do. 

 Because of the widespread exposure to nicotine in the human popula- 

 tion, it probably would be worthwhile to devote more attention to 

 potential mutagenic effects of nicotine. 



There are in cigarettes, also, substances which are known to be 

 carcinogens, and which have been the subject of much discussion in 

 recent years; benzpyrene is an example. On the general grounds that 

 many carcinogens are mutagens, these constituents of cigarettes also 

 deserve investigation. 



Certain additives to water supplies are worthy of mention, although 

 I think it very unlikely they could be significant as mutagens. Water 

 supplies are widely chlorinated, at a level of 0.2 to 0.4 mg/1. The 

 absorption of this chlorine in any significant amount can be discounted 

 because it reacts so avidly with organic material within the intestinal 

 tract. Mutagenesis by chlorine is an open question but, like some 

 other oxidizing agents, it might well have mutagenic actions in an iso- 

 lated system of cells. But this is a negligible hazard in human popu- 

 lations. 



Magni: It would be possible, anyway, to rule out this with a careful 



