Induction of micronuclei and toxic effects in embryos of pregnant rats treated before implantation with anticancer drugs: cyclophosphamide, cis-platinum, adriamycin.
To evaluate a possible relationship of maternal exposure to anticancer drugs during the preimplantation period to blastopathies and postimplantation embryotoxicity, CD female rats were injected intraperitoneally on day 3 of pregnancy with 15 and 30 mg/kg of cyclophosphamide (CPA), 2 and 4 mg/kg of Adriamycin (ADR), 3 and 6 mg/kg of cis-platinum (Cis-Pt), or with 5 ml/kg of saline. Blastocysts were collected on day 5 of gestation and evaluated for gross morphology, cell number, and micronuclei. Some females were sacrificed on day 21 of pregnancy in order to evaluate postimplantation embryotoxicity. A reduction in cell number/blastocyst was observed only in animals exposed to Cis-Pt 6 mg/kg; vice versa, a dose-related increase of micronuclei and of blastocysts with micronuclei was found in all groups treated with the anticancer agents. A significant increase of postimplantation loss was recorded in the groups treated with high doses of Cis-Pt and ADR, but no clear signs of teratogenicity were observed.
Giavini
E
E
Department of Biology, University of Milan, Italy.
Lemonica
I P
IP
Lou
Y
Y
Broccia
M L
ML
Prati
M
M
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D003520:Cyclophosphamide / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D008297:Male; D015162:Micronucleus Tests; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013723:Teratogens
D013723:Teratogens; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin