Ž . Mutation Research 431 1999 279–289 www.elsevier.comrlocatermolmut Community address: www.elsevier.comrlocatermutres Impact of maternal lifestyle factors on newborn HPRT mutant frequencies and molecular spectrum — Initial results from the ž / Prenatal Exposures and Preeclampsia Prevention PEPP Study William L. Bigbee a,b,c, ) , Richard D. Day c,d , Stephen G. Grant a,e , Phouthone Keohavong a,c , Liqiang Xi a , Lifang Zhang a , Roberta B. Ness b,c a Department of EnÕironmental and Occupational Health, Graduate School of Public Health, UniÕersity of Pittsburgh, Pittsburgh, PA 15238, USA b Department of Epidemiology, Graduate School of Public Health, UniÕersity of Pittsburgh, Pittsburgh, PA 15261, USA c Cancer Epidemiology Program, UniÕersity of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA d Department of Biostatistics, Graduate School of Public Health, UniÕersity of Pittsburgh, Pittsburgh, PA 15261, USA e Magee-Women’s Research Institute, Pittsburgh, PA 15213, USA Received 19 July 1999; received in revised form 30 August 1999; accepted 30 August 1999 Abstract Epidemiological studies have demonstrated associations between maternal tobacco smoke exposure and consumption of alcohol during pregnancy and increased risk of pediatric malignancies, particularly infant leukemias. Molecular evidence also suggests that somatic mutational events occurring during fetal hematopoiesis in utero can contribute to this process. As part of an ongoing multi-endpoint biomarker study of 2000 mothers and newborns, the HPRT T-lymphocyte cloning assay Ž . was used to determine mutant frequencies M in umbilical cord blood samples from an initial group of 60 neonates born to f a sociodemographically diverse cohort of mothers characterized with respect to age, ethnicity, socioeconomic status, and Ž . y6 y6 cigarette smoke and alcohol exposure. Non-zero M N s47 ranged from 0.19 to 5.62 =10 , median 0.70 =10 , f mean "SD 0.98 "0.95 =10 y6 . No significant difference in M was observed between female and male newborns. f Multivariable Poisson regression analysis revealed that increased HPRT M were significantly associated with maternal f w Ž . . consumption of alcohol at the beginning Relative Rate RR s1.84, 95% CI s0.99–3.40, P s0.052 and during Ž . pregnancy RR s2.99, 95% CI s1.14–7.84, P s0.026 . No independent effect of self-reported active maternal cigarette smoking, either at the beginning or throughout pregnancy, nor maternal passive exposure to cigarette smoke was observed. Although based on limited initial data, this is the first report of a positive association between maternal alcohol consumption during pregnancy and HPRT M in human newborns. In addition, the spectrum of mutations at the HPRT locus was f determined in 33 mutant clones derived from 19 newborns of mothers with no self-reported exposure to tobacco smoke and 14 newborns of mothers exposed passively or actively to cigarette smoke. In the unexposed group, alterations leading to ) Corresponding author. Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15238, USA. Tel.: q1-412-967-6534. Ž . E-mail address: wlbigbee@imap.pitt.edu W.L. Bigbee 0027-5107r99r$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. Ž . PII: S0027-5107 99 00172-4