Incorporation of zidovudine into leukocyte DNA from HIV-1-positive adults and pregnant women, and cord blood from infants exposed in utero.
OBJECTIVE
The nucleoside analog 3'-azido-3'-deoxythymidine (ZDV) has widespread clinical use but also is carcinogenic in newborn mice exposed to the drug in utero and becomes incorporated into newborn mouse DNA. This pilot study was designed to determine ZDV incorporation into human blood cell DNA from adults and newborn infants.


METHODS
In this prospective cohort study, peripheral blood mononuclear cells (PBMC) were obtained from 28 non-pregnant adults and 12 pregnant women given ZDV therapy, six non-pregnant adults with no exposure to ZDV, and six non-pregnant adults who last received ZDV > or = 6 months previously. In addition, cord blood leukocytes were obtained from 22 infants of HIV-1-positive, ZDV-exposed women and from 12 infants unexposed to ZDV. There were 11 mother-infant pairs involving HIV-1 -positive women.


METHODS
DNA was extracted from PBMC obtained from non-pregnant HIV-1-positive adults taking ZDV, pregnant HIV-1-positive women given ZDV during pregnancy, and from adults not taking ZDV. Cord blood leukocytes were examined from infants exposed to ZDV in utero and from unexposed controls. DNA samples were assayed for ZDV incorporation by anti-ZDV radioimmunoassay (RIA).


RESULTS
The majority (76%) of samples from ZDV-exposed individuals, pregnant women (8 of 12), non-pregnant adults (24 of 28), or infants at delivery (15 of 22), had detectable ZDV-DNA levels. The range of positive values for ZDV-treated adults and infants was 25-544 and 22-452 molecules ZDV/10(6) nucleotides, respectively. Analysis of 11 mother-infant pairs showed variable ZDV-DNA incorporation in both, with no correlation by pair or by duration of drug treatment during pregnancy. Two of the 24 samples from individuals designated as controls were positive by anti-ZDV RIA. The 20-fold range for ZDV-DNA values in both adults and infants suggested large interindividual differences in ZDV phosphorylation.


CONCLUSIONS
Incorporation of ZDV into DNA was detected in most of the samples from ZDV-exposed adults and infants. Therefore, the biologic significance of ZDV-DNA damage and potential subsequent events, such as mutagenicity, should be
Olivero
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OA
Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA.
Shearer
G M
GM
Chougnet
C A
CA
Kovacs
A A
AA
Landay
A L
AL
Baker
R
R
Stek
A M
AM
Khoury
M M
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Proia
L A
LA
Kessler
H A
HA
Sha
B E
BE
Tarone
R E
RE
Poirier
M C
MC
D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D015331:Cohort Studies; D004247:DNA / Q000097:blood / Q000378:metabolism*; D005260:Female; D005312:Fetal Blood; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000097:blood* / Q000188:drug therapy; D011446:Prospective Studies; D015215:Zidovudine / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015215:Zidovudine; D004247:DNA