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Transplacental effects of 3'-azido-2',3 -dideoxythymidine (AZT) : Tumorigenicity in mice and genotoxicity in mice and monkeys
Background: When given during pregnancy, the drug 3'-azido-2',3'-dideoxy-thymidine (AZT) substantially reduces maternal-fetal transmission of human immunodeficiency virus type 1 (HIV-1). However, AZT has been shown to be carcinogenic in adult mice after lifetime oral administration. In this study, we assessed the transplacental tumorigenic and genotoxic effects of AZT in the offspring of CD-1 mice and Erythrocebus patas monkeys given AZT orally during pregnancy. Methods: Pregnant mice were given daily doses of either 12.5 or 25.0 mg AZT on days 12 through 18 of gestation (last 37% of gestation period). Pregnant monkeys were given a daily dose of 10.0 mg AZT 5 days a week for the last 9.5-10 weeks of gestation (final 41%-43% of gestation period). AZT incorporation into nuclear and mitochondrial DNA and the length of chromosomal end (telomere) DNA were examined in multiple tissues of newborn mice and fetal monkeys. Additional mice were followed from birth and received no further treatment until subjected to necropsy and complete pathologic examination at 1 year of age. An anti-AZT radioimmunoassay was used to monitor AZT incorporation into DNA. Results: At 1 year of age, the offspring of AZT-treated mice exhibited statistically sig nificant, dose-dependent increases in tumor incidence and tumor multiplicity in the lungs, liver, and female reproductive organs. AZT incorporation into nuclear and mitochondrial DNA was detected in multiple organs of transplacentally exposed mice an
Oxford University Press
PMID : 9362158 ISSN : 0027-8874
Journal of the National Cancer Institute A. 1997, vol. 89, n° 21, pp. 1602-1608 [bibl. : 39 ref.]
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