The Induction of Germinal Mutations by Chemical Means

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Abstract
Approx. 50 germinal mutations involving coat color have been obtained in mice following the subcut. injn. of methylcholanthrene (both parents injd. at 60 days of age for 18 generations). This is a mutation rate of 1 in 557 mice (25,000 mice used in expt. either receiving methylcholanthrene or continued as untreated descent from exptl. animals). The controls of similar and unrelated origin, never subjected to methylcholanthrene, have shown a mutation rate of 1 to 26,250 mice, (8 mutations in 210,000 mice over a period of 27 yrs.). In addition to these clearcut cases of germinal mutations, there have also been obtained significant alterations in susceptibility to many induced tumors and these alterations of susceptibility have shown linkage with well-established genes such as brown and piebald, and sex. Thus it is reasonable to conclude that the effect of methylcholanthrene on the induction of tumors may be comparable to the effect of methylcholanthrene upon the germ plasm. Embryological disturbances such as dextrocardia, situs inversus and identical twins have also been obtained in the descendents of mice receiving methylcholanthrene over a number of generations. An increased prenatal mortality, alterations in sexual maturity, fertility and fecundity have also been observed. In 2 series of germinal mutations (of independent origin) obtained in this expt., there has been found a graded series of (a) mutant black (from brown), (b) pale black,(c) graphite, (d) dark gunmetal, (e) gunmetal, (f) darker bronze, (g) dark bronze, (h) bronze, (i) dark sepia, (j) sepia, (k) the original well-established brown, (l) chestnut, (m) light brown,(n) lighter brown,(o) velvet,and finally (p) buff. Each of these mutants breed true and they probably form a series of alleles at the brown-black locus. Many somatic mosaics have been obtained between 2 of the above mutant types, such as between chestnut and brown or brown and buff, etc. It is obvious that an unstable genetic state exists in these 2 lines, one of which was an outcross between the methylcholanthrene-injected series and C57 blacks, and the other, from a single litter of methylcholanthrene treated mice (without an outcross) in which 3 black mutants occurred in 7 young. Since a majority of the germinal mutations have occurred in these 2 descents (out of a total of 11 descents continued) the mutation rate from these 2 unstable genetic states is considerably higher than 1 in 557 estimated for the entire methylcholanthrene-injd. descent.

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