Carcinogenesis in tissue culture. 22. Malignant transformation of cloned rat liver cells treated in culture with 4-dimethylaminoazobenzene and properties of the transformed cells.

Cultured rat liver cells which were cloned from a single cell were transformed into malignant cells by a chemical carcinogen, 4-dimethylaminoazobenzene (DAB). The DAB-transformed cells produced tumors when back-transplanted into new-born rats but the carcinogen-untreated control cells did not. Characteristics of the transformed liver cells were compared to those of DABuntreated control cells in regard to the morphology, the consumption of DAB from the culture medium by the cells, the incorporation of 3H.DAB into the cells, and the aggregate.forming ability of the cells in rotation culture. The results showed that no significant parameter of malig. nant transformation in culture was detectable except the tumorigenicity of the transformed cells upon the inoculation into animals. ∗PMID: 4277389 [PubMed indexed for MEDLINE] Copyright c ©OKAYAMA UNIVERSITY MEDICAL SCHOOL Acta Med. Okayama 28,99-109 (1974 CARCINOGENESIS IN TISSUE CULTURE 22. MALIGNANT TRANSFORMATION OF CLONED RAT LIVER CELLS TREATED IN CULTURE WITH 4-DIMETHYLAMINOAZOBENZENE AND PROPERTIES OF THE TRANSFORMED CELLS MIYAHARA, Y., NAMBA, M. and SATO, j. Division of Pathology, Cancer Institute, Okayama University Medical School, Okayama, Japan. (Director: Prof. J. Sato.) Received for publication, November 8, 1973 Abstract: Cultured rat liver cells which were cloned from a single cell were transformed into malignant cells by a chemical carcinogen, 4-dimethylaminoazobenzene (DAB). The DAB-transformed cells produced tumors when back-transplanted into new-born rats but the carcinogen-untreated control cells did not. Characteristics of the transformed liver cells were compared to those of DAB-untreated control cells in regard to the morphology, the consumption of DAB from the culture medium by the cells, the incorporation of 3H.DAB into the cells, and the aggregate.forming ability of the cells in rotation culture. The results showed that no significant parameter of malig. nant transformation in culture was detectable except the tumorigenicity of the transformed cells upon the inoculation into animals. Cultured rat liver cells which were cloned from a single cell were transformed into malignant cells by a chemical carcinogen, 4-dimethylaminoazobenzene (DAB). The DAB-transformed cells produced tumors when back-transplanted into new-born rats but the carcinogen-untreated control cells did not. Characteristics of the transformed liver cells were compared to those of DAB-untreated control cells in regard to the morphology, the consumption of DAB from the culture medium by the cells, the incorporation of 3H.DAB into the cells, and the aggregate.forming ability of the cells in rotation culture. The results showed that no significant parameter of malig. nant transformation in culture was detectable except the tumorigenicity of the transformed cells upon the inoculation into animals. Either solid hepatoma or ascites hepatoma was produced by 4-dimethylaminoazobenzene (DAB) in rats (1, 2, 3). MILLER recently reviewed the biochemical mechanisms of the action of DAB on liver cells (4). There arise many difficulties in the studies of the mechanism concerned with chemical carcinogenesis in vizio; namely, 1) the selection of cells by treatment with drugs, 2) the monocellular mechanism of DAB-carinogenesis, and 3) the immune response of animals. For these reasons, the experiments regarding ma.1ignant transformation have been carried out by tissue cultures at the cellular level (5-15). In most of these studies were used fibroblast-like cells from mice and hamsters. KATSUTA and TAKAoKA treated liver cells with DAB in culture and found that the DAB-treatment during the first four days after explant induced a proliferation of resting rat liver cells (16). SATO confirmed a similar" proliferation-inducing activity" of 3'-methyl-DAB on rat liver cells in culture (17). He also stated that the liver cells transformed in culture by 3'-methyl-DAB produced tumors in the rats on back-transplantation of the cells (18, 19).