Effect of estrogen on induction of micronuclei by mutagens in male mice.
The effect of estrogen on the induction of micronucleated polychromatic erythrocytes (MPCE) by mutagens was examined in male mice. In the dose-response study, a dose-related inhibition of the mitomycin C (MMC)-induced MPCE frequency by estradiol (E2) treatment was observed. In the time study, inhibitory effects of E2 on MPCE frequency by MMC were observed when MMC was administered at 0 or 1 day after injection of E2. The most effective protocol for inhibition was when E2 and MMC were used on the same day. Of mutagens other than MMC, only vincristine (VCR) showed a significant decrease in MPCE frequency when used together with E2. Benzo[a]pyrene (BaP) and 5-fluorouracil (5-FU) showed no significant decrease in MPCE frequency. The data suggest that the induction of micronuclei by mutagens is inhibited by treatment with estrogen, and this could result in a sex difference in the sensitivity of mice employed in the micronucleus test. Mechanisms of the inhibitory effects of estrogen are discussed; these might include a suppression of erythropoiesis and a possible effect on the cell membrane permeability of erythroblasts.
Nagae
Y
Y
Drug Safety Laboratory, Ciba-Geigy (Japan) Ltd., Hyogo.
Miyamoto
H
H
Suzuki
Y
Y
Shimizu
H
H
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D002463:Cell Membrane Permeability / Q000187:drug effects; D004347:Drug Interactions; D004910:Erythrocyte Membrane / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D005472:Fluorouracil / Q000633:toxicity; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity*; D009153:Mutagens; D014750:Vincristine / Q000633:toxicity
D004967:Estrogens; D008937:Mitomycins; D009153:Mutagens; D001564:Benzo(a)pyrene; D016685:Mitomycin; D014750:Vincristine; D005472:Fluorouracil