Incorporation of zidovudine into cord blood DNA of infants and peripheral blood DNA of their HIV-1-positive mothers.
The nucleoside analogue 3'-azido-3'-deoxythymidine (AZT) is a weak carcinogen in adult female mice and a moderately strong carcinogen in the offspring of female mice given the drug during gestation. In addition, incorporation of AZT into DNA was observed in multiple organs of transplacentally exposed newborn mice. Here we investigate the incorporation of AZT into peripheral leukocyte DNA of HIV-1-positive adult pregnant women given AZT for variable times during gestation and cord blood of infants exposed to AZT in utero. The length of treatment varied between 10 days and 9 months. High molecular weight DNA was extracted from maternal peripheral blood mononuclear cells (PBMC) and infant cord blood. A specific AZT-DNA radioimmunoassay was used to determine the amount of AZT incorporated into leukocyte DNA. Incorporation of AZT into DNA ranged up to 183.3 and 344.5 molecules of AZT/10(6) nucleotides in the mothers and infants, respectively, and was detected in about 70% of samples. Therefore, AZT-induced mutagenic events are possible in the majority of adults and infants. No correlation was found between level of incorporation and length of AZT treatment, suggesting that the differences observed among the individuals arise from variability in AZT metabolism. These data support previous observations that a high degree of inter-individual variability in AZT phosphorylation occurs in primates.
Olivero
O A
OA
Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4255, Bethesda, Maryland 20892-4255, USA.
Shearer
G M
GM
Chougnet
C A
CA
Kovacs
A A
AA
Baker
R
R
Stek
A M
AM
Khoury
M M
MM
Poirier
M C
MC
D000328:Adult; D000818:Animals; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004247:DNA / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000635:transmission; D006679:HIV Seropositivity / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D007962:Leukocytes / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D051379:Mice; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015215:Zidovudine; D004247:DNA