HPRT gene alterations in umbilical cord blood T-lymphocytes in newborns of mothers exposed to tobacco smoke during pregnancy

Prenatal exposure to tobacco smoke has been associated with an increased risk of pediatric malignancies, yet the transplacental induction of genetic alterations by tobacco smoke carcinogens and their implication to childhood diseases remain poorly understood. We characterized mutations in the HPRT gene in umbilical cord blood T-lymphocytes of self-reported 103 never-smoking mothers and 104 smoking mothers (54 mothers smoked throughout and 50 mothers quit smoking during pregnancy). The results showed the illegitimate V(D)J recombinase-mediated deletion of HPRT exons 2-3 was the most prominent alteration occurring in 48.2% (26/54) of mutants from neonates of the smoking mothers who smoked during pregnancy, compared with 28.0% (14/50) from those of smoking mothers who quit smoking during pregnancy (p = 0.035, Fisher's exact test), 34.9% (36/103) from never-smoking mothers (p = 0.08), or 32.7% (50/153) of those of neonates born from the latter two groups of mothers combined (p = 0.043). There was no significant difference in the frequency of this deletion between neonates of the never-smoking mothers and the smoking mothers who quit smoking during pregnancy (34.9% versus 28.0%, respectively, p = 0.39). The results show an increase in illegitimate V(D)J recombinase-mediated deletion of HPRT exons 2-3 in cord blood T-lymphocytes of newborns of mothers who smoked during pregnancy, compared with the group of mothers who did not smoke during pregnancy, implying an increase in illegitimate V(D)J recombinase-mediated alteration, a genetic recombination event associated with childhood malignancies, may be induced in utero during pregnancy by maternal exposure to tobacco smoke-derived genotoxicants.