This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Columbano, A. Articles by Sarma, D. S. R. Search for Related Content PubMed PubMed Citation Articles by Columbano, A. Articles by Sarma, D. S. R.

Inability of Mitogen-induced Liver Hyperplasia to Support the Induction of Enzyme-altered Islands Induced by Liver Carcinogens¹

Istituto di Farmacologia e Patologia Biochimica, Universita di Cagliari, 09100 Cagliari, Italy [A. C., G. M. L-C.] and Department of Pathology, Medical Sciences Building, University of Toronto, Toronto, Ontario M5S 1A8, Canada [G. L., S. R., D. S. R. S.]

Experiments were designed to determine whether liver cell proliferation induced by direct mitogens is as effective as compensatory cell proliferation consequent to previous cell loss, in supporting the growth of enzyme-altered islands in the liver induced by chemical carcinogens. Male Wistar rats were given injections of a single nonnecrogenic dose of N-methyl-N-nitrosourea or benzo(a)pyrene during the S phase following the administration of four different liver mitogens, namely, lead nitrate, ethylene dibromide, nafenopin, and cyproterone acetate, or during compensatory cell proliferation following partial hepatectomy or a necrogenic dose of CCl₄. The carcinogen-altered hepatocytes were monitored as -glutamyltransferase- or placental glutathione S-transferase-positive foci using a 2-wk promoting regimen consisting of 0.03% 2-acetylaminofluorene coupled with a necrogenic dose of CCl₄. The results indicate that, unlike compensatory cell proliferation induced by partial hepatectomy or CCl₄, the mitogen-induced cell proliferation did not result in a significant number of enzyme-altered islands, despite the fact that the extent of cell proliferation at the time of carcinogen administration, as monitored by the examination of labeled cells, is similar with both types of proliferative stimuli.

¹ This investigation was supported by funds from USPHS Research Grants CA 23958 from the National Cancer Institute, C.N.R. (Medicina Preventiva e Riabilitativa No. 85.00509.56), Italy, and NATO (85/0184).

² To whom requests for reprints should be addressed, at Istituto di Farmacologia e Patologia Biochimica, Universita di Cagliari, Via Porcell 4, 09100 Cagliari, Italy.

Received 12/ 1/86. Revised 3/31/87. Revised 7/17/87. Accepted 7/22/87.

This article has been cited by other articles:

				G. M. Ledda-Columbano, A. Perra, D. Concas, C. Cossu, F. Molotzu, C. Sartori, H. Shinozuka, and A. Columbano Different Effects of the Liver Mitogens Triiodo-Thyronine and Ciprofibrate on the Development of Rat Hepatocellular Carcinoma Toxicol Pathol, January 1, 2003; 31(1): 113 - 120. [Abstract] [PDF]

				G. M. Ledda-Columbano, A. Perra, R. Loi, H. Shinozuka, and A. Columbano Cell Proliferation Induced by Triiodothyronine in Rat Liver Is Associated with Nodule Regression and Reduction of Hepatocellular Carcinomas Cancer Res., February 1, 2000; 60(3): 603 - 609. [Abstract] [Full Text]

				G.M. Ledda-Columbano, A. Perra, R. Piga, M. Pibiri, R. Loi, H. Shinozuka, and A. Columbano Cell proliferation induced by 3,3',5-triiodo-L-thyronine is associated with a reduction in the number of preneoplastic hepatic lesions Carcinogenesis, December 1, 1999; 20(12): 2299 - 2304. [Abstract] [Full Text] [PDF]