On the differential responsiveness of males and females in the micronucleus assay.
The primary question asked was whether the increased sensitivity of female mice to the induction of micronuclei by ethyl methanesulphonate, compared to males, would vanish if the doses were adjusted for any difference in the LD50 between the sexes. The second question was whether the frequency of micronuclei after 4 daily treatments would differ from 2 daily treatments. We measured the LD50 in the two sexes separately and found the female value to be lower. We also repeated the micronucleus measurements in each sex separately. At any given dose expressed in mg/kg the response in females was greater than in males. This was still true when the dose was expressed as a fraction of the LD50, but the difference was reduced. The uncertainty in the LD50 measurements was such that there may be no meaningful difference between males and females when the dose is expressed in this way. The 2-day and 4-day results differed very little for ethyl methanesulphonate, but were quite different for the positive control, dimethylbenz[a]anthracene, being higher at 4 days than at 2 days. We argue that the results of our experiments, which confirm the results of others, demonstrate the advisability of using both sexes in the assay.
Urlando
C
C
Bio-Mutatech Inc., York University Campus, Toronto, Ont., Canada.
Heddle
J A
JA
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005020:Ethyl Methanesulfonate / Q000633:toxicity*; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests / Q000379:methods*; D012016:Reference Values; D012737:Sex Factors
D015127:9,10-Dimethyl-1,2-benzanthracene; D005020:Ethyl Methanesulfonate