ALTERATION OF THE MICROSOMAL HEMOPROTEIN BY 3-METIIYLCHOLANTHRENE: EFFECTS OF ETHIONINE AND ACTINOMYCIN D

¹ The Wellcome Research Laboratories, Burroughs Wellcome & Co. (U.S.A.), Tuckahoe, New York

The ethyl isocyanide difference spectrum of microsomal hemoprotein from control or phenobarbital-treated rats exhibits spectral peaks at 455 mµ and 430 mµ whereas the spectrum of microsomal hemoprotein from rats treated with 3-methylcholanthrene (3-MC), 20 mg/kg/day for 3 days, exhibits peaks at 453 mµ and 430 mµ. Administration of 3-MC to rats also resulted in an increase in the ratio of the 455:430 absorption from 0.71 to 1.48 and a 6-fold increase in 3,4-benzpyrene hydroxylation. When ethionine or actinomycin D, inhibitors of protein synthesis, are administered prior to 3-MC, the increase in the ratio of 455:430 absorption, the shift in absorption maxima from 455 mµ to 453 mµ and the increase in 3,4-benzpyrene hydroxylation were blocked. The carbon monoxide difference spectrum of liver microsomes from control or phenobarbital-treated rats has a maximum absorption at 450 mµ Liver microsomes from 3-MC-treated rats exhibited a maximum absorption at 448 mµ. Administration of ethionine or actinomycin D, prior to 3-MC, prevented the shift in the 450-mµ peak to 448 mµ. Administration of methionine prevented the effects of ethionine. After solubilization of the microsomal hemoprotein with snake venom, the 450-mµ and the 448-mµ peaks seen with microsomes of untreated and 3-MC-treated rats, respectively, disappeared and the solubilized microsomal preparation from both untreated and 3-MC-treated rats, having a maximum absorption at 420 mµ only, became spectrally undistinguishable. These results show that pretreatment of rats with 3-MC causes changes in the spectral properties of the microsomal hemoprotein induced. These changes can be prevented by the administration of ethionine or actinomycin D, suggesting that 3-MC causes the synthesis of a spectrally different hemoprotein.

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