Studies on the mechanism of methylcholanthrene induction of enzyme activities

Abstract

The administration in vivo of 3-methylcholanthrene (MC) increases microsomal and ribosomal amino acid incorporation in vitro in rat liver. The microsomal amino acid incorporating system from MC-treated rats has the same cofactor requirements as does the normal preparation. Both preparations exhibit optimal incorporation at the same concentration of MgCl₂, GSH, and GTP and both preparations are equally sensitive to puromycin inhibition. The MC-induced increase in amino acid incorporation is due at least in part to an increase in the number of active microsomal incorporation sites and an apparent increase in the messenger-RNA content of the microsomes. The rate of loss of messenger RNA during a preincubation is the same in normal and MC microsomes. After removal of messenger RNA by preincubation, l-[¹⁴C]phenylalanine incorporation is completely dependent on added polyuridylic acid. In the presence of saturating levels of polyuridylic acid, the preincubated MC microsomes incorporate greater amounts of l-[¹⁴C]phenylalanine than do preincubated normal microsomes.

The MC effect on amino acid incorporation is paralleled by an MC-induced increase in the activity of liver benzpyrene hydroxylase. Administration of actinomycin-D prevents the stimulatory effect of MC on microsomal amino acid incorporation and on enzyme activity. The possible relationship between the effects of MC on the enzyme forming system and carcinogenesis are discussed.