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Oxidative DNA damage in mouse and monkey fetuses after transplacental exposure to AZT

  1. Author:
    Sipowicz, M. A.
    Diwan, B. A.
    Olivero, O. A.
    Poirier, M. C.
    Anderson, L. M.
    Kasprzak, K. S.
    1. Year of Conference: 1997
  2. Conference Name: Annual Meeting of the American Association for Cancer Research
    1. 38
    2. Pages: A3110
  4. Type of Work: Meeting Abstract
  1. Abstract:

    AZT (Azidothymidine) is widely prescribed for immunodeficient (HIV-positive) pregnant women, leading to concern that AZT could have toxic side effects in the fetus. In a test of oxidative fetal DNA damage, pregnant CD-1 mice were given AZT (25 mg/mouse/day) on gestation days 12 through 18. Fetal organs were assayed for the DNA nucleoside, 8-oxo-2'-deoxyguanosine (8-oxo-dG). Administration of AZT resulted in a significant 38% increase of 8-oxo-dG levels in fetal kidney as compared to untreated controls (1.3+/-0.1 vs 1.0+/- 0.1 8-oxo-dG/10(5) dG; P less than 0.03). In fetal liver 8-oxo-dG levels were also significantly higher (by 69%) in treated fetuses than in controls, 2.2+/- 0.3 vs 1.3 +/-0.1 (P less than 0.02). No significant differences were found in fetal lungs and brain. In a preliminary trial with a patas monkey fetus exposed transplacentally to a maternal dose of approx 1.5 mg/kg AZT 5x/wk for the last half of gestation (10 wks), average levels of 8-oxo-dG/10(5) dG in kidney, liver, lungs, and brain, 2.8+/-0.6, were greater than those in control fetal tissues (2.2+/-0.2; P=0.06). Greatest damage was in lung (4.7 vs 1.9), suggesting different tissue specificity compared with mouse fetuses. These results indicate oxidative DNA damage in both rodent and primate fetuses after in utero exposure to AZT.

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