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Properties of the Principal Liver Target Protein of a Hepatic Carcinogen¹

The Institute for Cancer Research, Fox Chase Center for Cancer and Medical Sciences, Philadelphia, Pennsylvania 19111

The lack of understanding concerning the mechanism of chemical carcinogenesis results in part from the absence of knowledge of the functional roles of the macromolecular targets of carcinogens in normal cells and the biological consequences of the interactions of the targets with carcinogens. The present study characterizes in part the principal liver target protein of the hepatic azocarcinogens.

The reaction of azocarcinogen with its principal target protein in liver during hepatocarcinogenesis in the rat caused no detected change in the molecular and subunit sizes and in the molecular charge of the target protein in liver cytosol. This conclusion is based on the observation that the immunologically detected target protein in normal liver cytosol is identical in these respects to the purified and characterized principal azoprotein of liver cytosol of rats fed azocarcinogen. The principal liver target protein, like the azoprotein, belongs to the electrophoretic class h₂ and the molecular size class 5S of liver cytosol proteins and has a subunit molecular weight of 44,000.

The rate of turnover of the principal liver target protein of the azocarcinogens resembles that previously reported for an average rat liver protein. The half-life of the target protein is 3.3 ± 0.1 (S.E.) days in livers of normal male adult rats given injections of guanido-¹⁴C-L-arginine, a marker that is minimally reincorporated into liver protein after degradation.

The implications of this identity and turnover rate are discussed in terms of the possible effects on the target protein that may result from its interaction with azocarcinogen during liver carcinogenesis.

¹ Supported in part by Grants CA-05945, CA-06927, and RR-05539 from the NIH, and an appropriation from the Commonwealth of Pennsylvania.

Received 3/22/74. Accepted 5/31/74.