Premium
Humans are a sensitive species to some of the biochemical effects of structural analogs of dioxin
Author(s) -
Lucier George W.
Publication year - 1991
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1002/etc.5620100604
Subject(s) - mechanism of action , receptor , toxicity , medicine , polychlorinated dibenzofurans , chemistry , cytochrome p450 , endocrinology , glucocorticoid receptor , isozyme , biology , enzyme , biochemistry , metabolism , environmental chemistry , in vitro
In 1979, rice oil contaminated with polychlorinated dibenzofurans (PCDFs) was ingested in a widespread poisoning episode in Taiwan. The PCDFs are structural analogs of 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD). TCDD and the PCDFs are thought to share the same mechanism of action that involves binding to the Ah receptor. In our studies, we compared the effects of TCDD on rat liver to effects in placentas of women exposed to PCDF‐contaminated rice oil. TCDD is a hepatocarcinogen in female rats. Measured parameters included concentrations of human placental PCDF congeners or rat liver TCDD and induction of cytochrome P‐450 isozymes, epidermal growth factor receptor (EGFR) and glucocorticoid receptor (GCR). Placentas from PCDF‐exposed women contained two PCDFs: 2,3,4,7,8‐penta CDF (100 ppt) and 1,2,3,4,7,8‐hexa CDF (400 ppt). The 2,3,4,7,8‐penta CDF binds the Ah receptor 60% as well as TCDD, and the 1,2,4,7,8‐hexa CDF binds 9% as well as TCDD. Cytochrome P 1 ‐450 was induced approximately 100‐fold in exposed placentas. This induction was considered maximal. Placental PCDF concentrations associated with this induction were compared to the amount of hepatic TCDD required to maximally induce the rat liver homolog of P 1 ‐450. These comparisons, accounting for differences in Ah receptor binding, suggested that humans are more sensitive than rats to the P 1 ‐450 inductive actions of the toxic halogenated aromatics. Several assumptions are made, and their validity is discussed. As with the P 1 ‐450, humans are more sensitive to the effects of the halogenated aromatics on EGFR (EGF‐stimulated autophosphorylation) and GCR (binding capacity) than are rats. Although the relationship of these biochemical changes to the carcinogenic effects of TCDD and its analogs is not clear, our data suggest that it is prudent to retain a conservative risk assessment for the toxic halogenated aromatics.