Transplacental incorporation of 3'-azido-2',3'-dideoxythymidine(AZT) into DNA of fetal CD-1 mice and Erythrocebus patas monkeys (Meeting abstract).

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Transplacental incorporation of 3'-azido-2',3'-dideoxythymidine(AZT) into DNA of fetal CD-1 mice and Erythrocebus patas monkeys (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 38:A2372 1997. Unique Identifier : AIDSLINE ICDB/98639372
Olivero OA; Anderson LM; Diwan BA; Rice JM; Yuspa SH; Laing CP; Chang PK; Jones AB; Poirier MC; LCCTP,NCI,NIH, Bethesda, MD 20892

Abstract: AZT administration to reduce fetal transmission of HIV in human pregnancy is highly effective and currently in widespread clinical use. In order to explore possible toxic effects to the fetus, AZT incorporation was investigated in fetal DNA of monkeys and mice exposed during gestation. Two pregnant Erythrocebus patas monkeys were given 1.5 mg AZT/kg body weight 5 times per week orally during the last half of pregnancy. AZT incorporation into mitochondrial and nuclear DNA was observed in placenta, maternal liver and blood and various fetal tissues, using an anti-AZT radioimmunoassay. Incorporation of AZT into fetal nuclear and mitochondrial DNA was seen in multiple monkey tissues with values of incorporation ranging between 0.2 and 1.5 AZT molecules/10(6) nucleotides. Three pregnant CD-1 mice were given AZT, (25 mg/mouse/day), on days 12 to 18 of gestation. AZT-DNA incorporation was determined in both nuclear and mitochondrial DNA from fetal brain, kidney, liver, lung and skin, and ranged from 0.1 and 0.7 AZT molecules/10(6) nucleotides in these organs. The data demonstrate that AZT crosses the placenta causing widespread fetal genotoxicity, and suggest that the drug targets mitochondrial as well as nuclear DNA. Therefore it is possible that AZT will be incorporated into human fetal DNA resulting in toxic effects to the fetus.

Keywords: Animal DNA Damage DNA, Mitochondrial/DRUG EFFECTS/*METABOLISM *Erythrocebus patas Fetus/*DRUG EFFECTS Placenta/METABOLISM Zidovudine/*PHARMACOKINETICS ABSTRACT
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M9820753

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