Genotoxic impact in human newborns of maternal exposures and lifestyle factors during pregnancy

The purpose of this study was to determine the genotoxic effects in human newborns resulting from maternal exposures to xenobiotics during pregnancy. Two separate population studies were performed to assess the genotoxic impact of two different exposures (AZT and tobacco smoke) in pregnant women, by measuring DNA damage in newborn umbilical cord blood cells using the Comet Assay, as a biomarker of effect.; Human lymphoblastoid H9 cells were exposed during log growth to 0.05–1.2 mM AZT for 24 hours. Cell viability, cell cycle progression, and incorporation of AZT into DNA were determined. DNA damage was quantified using the Comet Assay. Under these conditions, viability was greater than or equal to 80%. At the higher concentrations, AZT induced S phase cell cycle arrest and growth inhibition in parallel with increased AZT/DNA incorporation. AZT-treated cells exhibited a dose-dependent increase in DNA migration in the Comet Assay when electrophoresed under pH > 13 alkaline conditions (P < 0.001).; Using the alkaline (pH > 13) Comet Assay, two population-based studies were performed. The first population study assessed the genotoxic impact of AZT and other dideoxynucleoside analogues in pregnant women; the second study assessed the genotoxic impact of tobacco smoke products in pregnant women by measuring the level of DNA damage in newborn umbilical cord blood. There was not a statistically significant difference in DNA migration between blood cells sampled from newborns of women exposed to AZT and newborns of untreated women [group mean tail moment (TM) of 22.7 ± 14.8 (SD) versus 21.2 ± 10.7, respectively; P = 0.60]. Also, we did not find a statistically significant difference in DNA migration between blood cells of newborns of women who smoked during pregnancy and newborns of non-smoking women (TM of 8.8 ± 8.5 versus 9.2 ± 8.4, respectively; P = 0.73). Overall, these results demonstrate that the genotoxic impact in newborns of transplacental exposure to the levels of AZT and tobacco smoke received by the maternal subjects in this study are both small compared to the sum of the effects of environmental xenobiotic exposures and endogenous genotoxic mechanisms that contribute to the overall background level of DNA damage detected by the Comet Assay in umbilical cord blood cells. (Abstract shortened by UMI.)...