SENSITIVITY OF SOMATIC MUTATIONS IN HUMAN UMBILICAL-CORD BLOOD TO MATERNAL ENVIRONMENTS

Citation
Dk. Manchester et al., SENSITIVITY OF SOMATIC MUTATIONS IN HUMAN UMBILICAL-CORD BLOOD TO MATERNAL ENVIRONMENTS, Environmental and molecular mutagenesis, 26(3), 1995, pp. 203-212
Citations number
43
Categorie Soggetti
Environmental Sciences","Genetics & Heredity
ISSN journal
08936692
Volume
26
Issue
3
Year of publication
1995
Pages
203 - 212
Database
ISI
SICI code
0893-6692(1995)26:3<203:SOSMIH>2.0.ZU;2-5
Abstract
To assess the potential effect of maternal environments on human embry onic/fetal somatic mutation, we measured the frequencies of hypoxanthi ne-guanine phosphoribosyltransferase (HPRT, hprt gene), mutant T lymph ocytes (M(f)), and glycophorin A (GPA) variant erythrocybs (V-f) of bo th allele-loss (empty set/N) and allele-loss-and-duplication (N/N) phe notypes in umbilical cord blood. The mean hprt M(f) (1.40 +/- 1.11 X 1 0(-6), N = 66) and GPA V-f (empty set/N 4.0 +/- 2.2 X 10(-6), N = 114; N/N 2.7 +/- 2.0 X 10(-6), N = 91) were significantly lower than those previously reported for adult populations. In addition, the hprt M(f) was significantly higher than that of a published study of newborn co rd blood samples from a geographically distant population (0.64 +/- 0. 41 x 10(-6), N = 45, P < 0.01; t test, P < 0.01, Mann-Whitney U test). An examination of the demographic data from these two populations led to the sampling of 10 additional newborns specifically matched to the published study for maternal socioeconomic status. The hprt M(f) (0.7 0 +/- 0.49 x 10(-6)) of this selected population was consistent with t he published report and significantly lower than that of our initial p opulation (P < 0.03, t test; P < 0.01, Mann-Whitney U test). These res ults indicate that there is an environmental effect related to materna l socioeconomic status on the frequency of embryonic/fetal somatic mut ations. Molecular analyses of hprt mutants from this cohort with eleva ted M(f) revealed a significant decrease in the relative contribution of gross structural mutations to the overall M(f) (25 of 38, 66% vs. 3 4 of 41, 83%, P = 0.024, chi(2) test), suggesting that the higher Mi r esulted from an elevated level of ''point'' mutations. No individual m aternal demographic or environmental factor was identified as contribu ting more significantly than other any factor to the observed variabil ity in hprt M(f) or GPA V-f. (C) 1995 Wiley-Liss, inc.