172 MUTATIONS 



antiseptic. It is taken by mouth and absorbed well, and it ends in the 

 bladder where, provided the urine is acidified, there is a release of 

 ammonia and formaldehyde. Formaldehyde is clearly mutagenic in 

 some systems. But we do not know the extent to which formaldehyde 

 released in the bladder, or the smaller amounts released during the 

 passage of methenamine through the blood, may have access to the 

 germ cell. Equally unknown is whether the formaldehyde in the blad- 

 der may ever be carcinogenic. 



Another compound of interest is paraldehyde, which is a trimer of 

 acetaldehyde. It is a sedative, often used in manic alcoholics. It is 

 injected intravenously in very considerable doses, and has an excellent 

 sedative action. But its metabolism in the body is at least in part a 

 breakdown of the trimer to release acetaldehyde. 



Atwood: Why is it so nontoxic if it makes acetaldehyde? 



Goldstein: The acetaldehyde levels are very low. Right now I am 

 not concerned with quantities but only with pointing out that these 

 drugs exist, and that they (or their metabolites) belong to certain 

 classes that are known to be mutagenic. It may very well be, from 

 the standpoint of practical mutagenesis, that the amounts involved 

 are absolutely negligible. 



Auerbach: Rapoport (49) found that acetaldehyde is a much weaker 

 mutagen than formaldehyde. 



Goldstein: It has not been adequately tested in other systems (18) . 



There is also chloral hydrate, which was, and in some places still 

 is, a very popular hypnotic agent, so that a great many people have 

 been exposed. This drug is a hydrated form of trichloracetaldehyde. It 

 is a spindle poison and mutagen (5). 



Phenols have been shown to have mutagenic effects, and a great 

 many drugs, as you might expect, are phenols. I am not clear to what 

 extent the phenol group in itself confers mutagenic. action or whether 

 only the simple phenols and cresols that have been investigated are 

 mutagenic. 



Examples of naturally occurring phenols are the catechols, such as 

 epinephrine. Many complex drug molecules such as morphine contain 

 a phenolic group, and — 



Novick: Also, tyrosine. 



Goldstein: Yes, tyrosine is a naturally occurring one. Now, a few 

 words about nitrites. Nitrous acid is well established to be a potent 

 mutagen. Sodium nitrite is still used as a preservative in certain kinds of 

 food, particularly in meats, where it is accepted as safe on the basis 

 of ordinary toxicity considerations. However, in the acid environment 



