auerbach: effects of chemicals 123 



melamine (TEM) proved a much more suitable mutagen for mice 

 (16). Very high frequencies of dominant lethals and translocations 

 were obtained after intraperitoneal injection. One translocation is 

 of particular interest because it produces a position effect on two 

 recessive coat color genes in the neighborhood of the break. Both of 

 these genes, when present in heterozygous combination with the 

 translocation, give a flecked pattern (17). Position effects had pre- 

 viously not been known in mice. Curiously enough, at the same time, 

 several similar ones were found among X-ray-induced translocations 

 (80). 



A different method for testing mutagens on mammalian cells has 

 been developed by Klein and Klein (52) and, independently, by 

 Mitchison (61). It has been used in our Institute for testing TEM (27). 

 Tumors are induced in hybrids between two inbred strains of mice 

 which are isogenic apart from one allelic difference at the histo- 

 compatibility locus. The hybrid tumors, possessing both antigens, 

 will not take in either parental strain unless they have lost one of the 

 antigens. The frequency with which this happens could be increased 

 by TEM. Whether the underlying event is mutation proper, chromo- 

 some loss, deficiency, or somatic crossing-over could not be decided. 



It is customary to interpret the effects of alkylating agents in 

 terms of interaction with DNA. This may be correct, but it is not 

 proved. The fact that the DNA, the transforming principle, is 

 exceedingly sensitive to the destructive action of mustard gas (45) 

 does not necessarily imply that the primary attack of mustard gas as a 

 mutagen must be on DNA. Some evidence in favor of this assumption 

 has recently been provided by the finding (58) that several alkylating 

 agents, in particular ethyl methanesulphonate, can produce mutations 

 in bacteriophage treated in vitro. 



Whatever its point of attack, mustard gas, like X-rays, act in a 

 "hit"-wise fashion, that is, it produces mutations and chromosome 

 breaks by independent reactions that affect separate points in a 

 more or less random fashion. For X-rays this was established by stud- 

 ies of dose-effect relations. Evidence of this type is not easy to obtain 

 for the action of chemicals on a complex organism. For certain muta- 

 gens a linear relationship between dose and effect has been shown 

 to hold good within rather narrow ranges of cencentration (33, 42), 

 but this finding is open to different interpretations. In particular, it 



