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Use of fetal cell culture as an experimental system for predicting drug metabolism in the intact animal
Author(s) -
Nebert Daniel W.
Publication year - 1973
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1973144part2693
Subject(s) - toxicity , in vivo , strain (injury) , pyrene , metabolism , enzyme inducer , enzyme , xenobiotic , biochemistry , cell culture , biology , drug metabolism , fetus , chemistry , genetics , anatomy , pregnancy , organic chemistry
The extent of aryl hydrocarbon (benzo[a]pyrene) hydroxylase induction in various tissues of ten inbred strains of mice by aromatic hydrocarbon administration in vivo is correlated (0.02 < p < 0.05) with the magnitude of hydroxylase induction in fetal cell cultures derived from that strain. The enzyme causes the formation of highly reactive and therefore toxic polycycliC hydrocarbon epoxides and phenols. The toxicity of aromatic hydrocarbons in vivo and in cell culture is greater for the C57BL/6N mouse strain, in which the hydroxylase is inducible, than for the DBA/2N strain, in which the enzyme is virtually noninducible. Therefore, the degree of toxicity of aromatic hydrocarbons in fetal cell culture reflects in large part the toxicity of polycylic hydrocarbons in the intact animal and in turn reflects the genetically regulated response of the individual to the foreign compound. It is speculated that the teratogenicity of various drugs or other xenobiotics in a certain strain or species of animal may likewise be predicted, if one is able to quantitate certain parameters of a compound's metabolism in fetal cell cultures from that particular strain or species.