Placental markers of human exposure to polychlorinated dibenzofurans and polychlorinated biphenyls: implications for risk assessment.
In 1979, rice oil accidentally contaminated with a mixture of polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) was ingested by a large number of individuals in Taiwan. Placentas obtained from women four years after the exposure had occurred contained several PCB congeners known to be present in the rice oil as well as two toxic PCDF congeners: 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran (1,2,3,4,7,8-HCDF). Placentas from exposed women had markedly elevated activities of two cytochrome P1-450 dependent enzymes, arylhydrocarbon hydroxylase and ethoxyresorufin O-deethylase. The average magnitude of enzyme induction was 100-fold, but much interindividual variation was evident. Binding properties of epidermal growth factor (EGF) to its receptor were not altered by PCB-PCDF exposure. However, EGF-stimulated autophosphorylation of the EGF receptor was decreased significantly in placentas from exposed women and this effect was strongly correlated with decreased birth weight. Species comparisons of effects on EGF receptor actions and cytochrome P-450 isoenzymes, coupled with data on tissue concentrations of PCDFs, suggest that humans are more sensitive than rats to some of the biochemical effects of PCDFs and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The data are discussed in relation to key issues in the risk assessment of the toxic halogenated aromatics.
Lucier
G W
GW
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Sunahara
G I
GI
Wong
T K
TK
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001572:Benzofurans / Q000032:analysis / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002274:Carcinogens, Environmental / Q000032:analysis / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000378:metabolism; D005260:Female; D005506:Food Contamination; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D012275:Oryza; D010088:Oxidoreductases / Q000378:metabolism; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D010938:Plant Oils; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism; D051381:Rats; D012306:Risk; D013045:Species Specificity
D001572:Benzofurans; D014408:Biomarkers, Tumor; D002274:Carcinogens, Environmental; D010938:Plant Oils; D000072317:Polychlorinated Dibenzodioxins; C023614:dibenzofuran; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1