Evidence that 2‐allyl‐2‐isopropylacetamide, phenobarbital and 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine induce the same cytochrome P450 mRNA in chick embryo liver

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Abstract
The induction of cytochrome P450 in chick embryo liver was studied using 3 different porphyrinogenic drugs, 2-allyl-2-isopropylacetamide, 3,5-diethoxycarbonyl-1,4-dihydrocollidine and phenobarbital. Pulse-labeling studies showed that for each drug the cytochrome P450 synthesized either in ovo or in a wheat germ translation system reacted immunologically with antibody raised against the purified 2-allyl-2-isopropylacetamide-induced enzyme (MW = 50,000). To investigate whether this is due to the 3 drugs inducing the same protein or different proteins with common immunological determinants, nucleic acid hybridization studies were carried out using a recently characterized 2-allyl-2-isopropylacetamide-induced cytochrome P450 cloned cDNA probe. The mRNA induced by each drug hybridizes with this probe and all are of similar size. The melting profile of the mRNA .cntdot. c[complimentary]DNA hybrids indicates that the mRNAs induced by the 3 drugs have at least 98% homology with the cDNA probe. Restriction endonuclease digestions of total chick embryo genomal DNA and a chick cytochrome P450 genomal clone indicates that the cytochrome P450 gene homologous with the cDNA probe is represented in the genome only once. Evidently, the 3 drugs cause increased levels of the same cytochrome P450 mRNA, possibly due to enhanced expression of the same gene. Other cytochrome-P450-inducing drugs, 3-methylcholanthrene, .beta.-naphthoflavone or pregnenolone-16.alpha.-carbonitrile do not increase the level of the 2-allyl-2-isopropylacetamide-inducible mRNA but rather reduce it to a level which was lower than that of the untreated controls.

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