Effects of carcinogens and other agents on histone methylation in rat liver nuclei by endogenous histone lysine methyltransferase.

inhibited by S-adenosyl-L-ethionine. The endogenous methyltransferase was able to transfer ethyl groups from the latter compound to histone but with very low efficiencycompared to the arginine methyltransferase reported previ ously. The histone lysine methyltransferase has a Km value of 3.0 /IM, and the K, value for S-adenosylethionine inhibition is 0.17 mM. Product inhibition by S-adenosylhomocysteine (K, = 12 //M) was also observed. Histone methylation in nuclei in vitro is sensitive to activated or unstable carcinogens but insensitive to inhibition by many carcinogenic agents which have been proposed to require enzymatic activation in vivo and to inhibitors of transfer RNA methyltransferases. The implications of these find ings for the mechanism proposed previously by which carcinogenic agents induce neoplastic transformation are discussed.