Urea Synthesis in Novikoff and Morris Hepatomas1

found that N-acetyl-L-glutamate-dependent CPS l@ EEC 2.7.2.5 (NH4)], one of the 1st steps in the pathway of urea synthesis, was retained in varying degrees in welland highly differentiated tumors (14). There was also a marked lowering of CPS I activity in the livers of rats bearing large, slow-growing tumors with high CPS I activity (21, 28A, 44, 47C, and 5123C). These findings confirm and extend pre vious results reported by Ono et a!. (25). Further exploration of this phenomenon revealed that the decline in the level of CPS I activity was inversely related to the size of the tumor; as the CPS I-containing tumors grew larger, liver CPS I activity decreased, to maintain a relatively constant total of CPS I activity in the host animals. The effect was not ob served in rats bearing either fast-growing hepatomas on slow-growing hepatomas with low CPS I activity, and thus it was not due to some nonspecific nutritional effects of the tumor on the host. Since CPS I represents an essential step in a vital hepatic function, namely, urea synthesis, we have extended our studies to investigate matesof urea synthesis in a series of Morris hepatomas and in the Novikoff hepatoma, using a tissue slice system, to determine the possible physiological significance of the decline in CPS I activity in the livers of rats beaning slow-growing hepatomas. Earlier studies by Greenstein (8), with slices of transplanted hepatomas, and Weil-Maherbe and Dickens (38), with slices from 3'-methyl 4-d imethylaminoazobenzene-i nduced primary hepatomas, failed to demonstrate synthesis of urea by these tumors. Therefore, this study represents the 1st report of urea syn thesis by rat liven neoplasms.