Malignant Transformation in vitro of Rat Liver Cells by Dimethylnitrosamine and N-Methyl-N′-nitro-N-Nitrosoguanidine

Abstract

Summary.-Epithelial-like cells originating from 10-day and 8-week old BD rats were treated in vitro with dimethylnitrosamine (DMN) and N-methyl-N'-nitronitrosoguanidine (MNNG). Morphologically, no differences were seen between treated and untreated cells up to the time when the cells were transplanted into syngeneic hosts. However, the treated cells grew in soft agar and once injected subcutaneously or intraperitoneally into newborn rats, developed tumours after a latent period of 9-12 weeks. The tumours obtained with DMN-treated cells were well differentiated adenocarcinomata, whereas carcinosarcomata were observed with the MNNG-treated cells.

Surface proteins in normal and transformed rat liver epithelial cells in culture

“…ID). As shown in the Table, the long-term cultures also include tumorigenic cells, as indicated by the development of tumours after inoculation of these cells into syngeneic rats, and by certain in vitro changes, such as capacity to grow in soft agar and the appearance of specific markers like y-glutamyl transpeptidase (Montesano et al, 1973(Montesano et al, , 1975(Montesano et al, , 1977Kuroki et al, 1976;Huberman et al, 1979). The show a spindle-like morphology in culture (see Montesano et al, 1975Montesano et al, , 1977 (Fig.…”

“…A long-term culture of epithelial liver cells was established and maintained as previously described (Montesano et al, 1973(Montesano et al, , 1975(Montesano et al, , 1977 or was established from primary cultures of epithelial liver cells obtained after perfusion, as described above. Rat hepatoma lines 8994-112 and 7777-165 were kindly supplied by Dr B. de Nichaud (Institut Scientifique de la Recherche sur le Cancer, Villejuif, France) and maintained as previously described (Becker et al, 1976).…”

In vitro assay of cytotoxicity with cultured liver: accomplishments and possibilities.

“…Malignant transformation of cultured hepatic epithelial cells has been accomplished by several investigators by exposing cells in vitro to several chemical carcinogens (77)(78)(79)(80)(81)(82)(83), as well as to SV-40 virus (58). These studies demonstrated that transformed hepatic epithelial cells, when strains or "pure" lines are used, produce adenocarcinomas on back-transplantation into isogeneic animals and not sarcomas, as is the situation with transformed fibroblasts.…”

“…These studies demonstrated that transformed hepatic epithelial cells, when strains or "pure" lines are used, produce adenocarcinomas on back-transplantation into isogeneic animals and not sarcomas, as is the situation with transformed fibroblasts. Chemical transformants from some nonclonally derived hepatic epithelial cell lines have produced sarcomas-or carcinosarcomas on back transplantation, reflecting the fact that these cultures included a mixed population of epithelial and mesenchymal cells (79). Carcinogens successfully employed to transform hepatic epithelial cells in vitro are dimethylnitrosamine (78,79,82), Nmethyl-N'-nitro-N-nitrosoguanidine (79,82), Nmethyl-N-nitrosourea (78,79,82), N-hydroxyacetylaminofluorene (78), N-acetoxyacetylaminofluorene (81), 4-nitroquinoline-N-oxide (77), aflatoxin B1 (78, 80), 3-methylcholanthrene (81), 3-methyldimethylaminoazobenzene (81), 7,12-dimethylbenzanthracene (78), benzo(a)pyrene (83), and methylazoxymethanol (83).…”

Surface antigens of rat liver epithelial cells grown in medium containing foetal bovine serum

“…Although epithelial cells are less readily transformed in vitro, it has been reported that rat liver cells cultured for long periods could be transformed by a number of carcinogens (Williams et at., 1973;Montesano et al, 1973;Jype, 1974;Borenfreund et al, 1975). Similarly epidermal cell transformation also has been demonstrated in vitro (Fusenig et al, 1973;Colburn et al, 1978).…”