Toxicology of environmentally persistent chemicals: mirex and chlordecone

摘要

Mirex and chlordecone are structurally similar organochlorine insecticides that are chemically and biologically stable and, concequently, broadly distributed in the environment. Although chemically similar with similar effects on the nervous system, their interactions with other biological systems may be quite different. For example, while both chemicals are believed to be environmental estrogens, chlordecone interacts with the estrogen receptors while mirex does not. Similarly, mirex is a unique tumor promoter in the mouse skin model while chlordecone is not. chlordecone dramatically potentiates the hepatotoxicity of carbon tetrachloride while mirex does not. Mirex, on the other hand, causes cataracts in young rats following exposure of the dams while chlordecone does not. Both mirex and chlordecone are known to be potent cytochrome P450 inducers and recent studies have been directed toward definition of the isoform specificity of this induction. On acute dosing of mice and based on substrate level oxidation. Western blotting and RT-PCR, it has been shown that CYPs 2B10, 1A2 and 3A are induced, although there are both chemical related differences and gender differences. On chronic dosing, in addition to the above CYP isoforms, CYP2E1 is also induced in mouse liver. The relationship of this induction to testosterone metabolism has also been investigated and CYP 3A25, a CYP isoform involved in the #beta#-hydroxylation of testosterone has been cloned, sequenced, expressed in E. coli and characterized.