Role of maternal exposures and newborn genotypes on newborn chromosome aberration frequencies.
Maternal exposures may induce chromosome damage and birth defects in the fetus. Polymorphic variation in genes coding for enzymes involved in metabolic activation and detoxification of environmental procarcinogens may account for some of the differences in chromosome aberration frequencies in newborns. In this study, 40 mothers completed questionnaires regarding exposures they received during their pregnancy. Umbilical cord blood samples were analyzed for chromosome aberrations. An average of 1020 metaphase cell equivalents (equal to 1020 G-banded cells) were examined from each newborn. In 26 of the newborns, genotyping analysis was performed for genes functioning in metabolic activation and detoxification (cytochrome P450 genes: CYP2D6 and CYP1A1, and phase II genes: NAT1, NAT2, GSTT1, GSTM1, GSTP1, and epoxide hydrolase). A significant association between the CYP1A1 MspI polymorphism and chromosome aberration frequencies was observed in the newborns (p=0.02), with heterozygotes showing higher aberration frequencies than the wild type homozygotes. Some large differences in chromosome aberration frequencies for other genotypes were also noted, but these were not statistically significant. Exposure to tobacco smoke in utero also appeared to increase translocation frequencies. The mean frequency of translocations per 100 cell equivalents from newborns of mothers who smoked during pregnancy was significantly higher than that of newborns whose mothers did not smoke (0.21 vs. 0.11, respectively, p=0.045).
Pluth
J M
JM
Radiation Oncology Department, Stanford University, Cancer Biology Research Laboratory, GK109, Palo Alto, CA 94305, USA.
Ramsey
M J
MJ
Tucker
J D
JD
D000123:Acetyltransferases / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002274:Carcinogens, Environmental / Q000378:metabolism / Q000633:toxicity; D002869:Chromosome Aberrations; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004781:Environmental Exposure; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires
D002274:Carcinogens, Environmental; D019363:Cytochrome P-450 CYP1A1; D019389:Cytochrome P-450 CYP2D6; D000123:Acetyltransferases; D005982:Glutathione Transferase