AIR POLLUTION EFFECTS ON WOMEN AND DEVELOPING FETUS

Prevention of environmentally related cancer will be enhanced by understanding etiologic mechanisms and in particular by identifying genetic, acquired, or developmental factors that place subgroups of the population at greatest risk. The proposed research aims to validate promising biomarkers of exposure, response, and susceptibility in two groups of Polish women and their newborn infants: urban women exposed to polycyclic aromatic hydrocarbons (PAH) and associated air pollutants at levels 1O-fold higher than those found in U.S. cities, but below most workplace levels, and rural women from a non-polluted area. Because many of these carcinogens appear to have no "threshold" for biological effects, once these biomarkers are validated they can be incorporated into epidemiologic studies of industrial and urban air pollution in the U.S. and elsewhere. During the winter of 1992 samples of placental tissue, infant cord blood and maternal peripheral blood were collected from mother/newborn pairs along with information on potential confounding factors. The biological samples were immediately processed, transported on liquid nitrogen or dry ice to Columbia University and stored at -196 degrees C (lymphocytes) or --70 degrees C (buffy coat, plasma and placental tissue). In this interinstitutional laboratory analysis of shared specimens, the biomarkers to be assessed include PAH-DNA adducts by enzyme-linked immunosorbent assay (ELISA) and aromatic-DNA adducts by 32P-postlabeling (markers of biologically effective dose), the frequency of gene mutation at the hprt locus in T-lymphocytes (a marker of biologic response), aryl hydrocarbon hydroxylase (AHM) activity, glutathione-S-transferase genotype (GSTm1),and CYP1A1 MSP1 polymorphism (markers of genetic/metabolic susceptibility). All of the biomarkers are biologically relevant to carcinogenesis in general and are not restricted to cancers of the lung or to the inhalation route. The following research questions will be addressed: 1) the relationship between air pollution exposure and markers of biologically effective dose and biologic response, adjusting for age, smoking, occupational and dietary exposures 2) ability of genetic/metabolic markers (AHH activity, GSTm1 genotype, CYP1A1 Msp1 polymorphism ) to modify these markers 3) comparison of the same biomarkers in maternal and fetal/newborn tissues 4) comparison of DNA adducts in placental tissue versus cord blood from newborns; 5) overall feasibility of each biomarker for future epidemiologic research in environmental carcinogenesis. Answers to these questions will facilitate the development of strategies for preventing environmentally-induced cancers.