Rat hepatoma

Uracil is used more effectively, in nucleic acid synthesis within a rat hepatoma than in normal liver. This observation appears to have stimulated the synthesis of 5-fluorouracil (1027) as an antimetabolite mainly because the introduction of a fluorine atom involves a minimal increase in size. In the event, 5-fluorouracil did prove to have antineoplastic activity and it is now a valuable drug for treatment of tumors of the breast, colon or rectum, and to a lesser extent, gastric, hepatic, pancreatic, uterine, ovarian and bladder carcinomas. As with other drugs which interfere with DNA synthesis, the therapeutic index is quite low and great care is required during treatment (69MI21301). 

Sensitivity of cancerous cells to copper may reflect cell DNA content. Two closely related rat hepatoma cell lines differed in sensitivity to copper toxicity by a factor of four DNA content in each cell line decreased with increasing copper concentrations, but at different rates. Severity of toxicity was associated with increasing accumulations of copper in the cell nucleus and with decreasing DNA (Toussaint and Nederbragt 1993). 

Toussaint, M.J.M. and H. Nederbragt. 1993. Copper and zinc toxicity in two rat hepatoma cell lines varying in differentiation. Comp. Biochem. Physiol. 104C 253-262. 

Tributyltins and other organotins induce chromosomal aberrations in mammals, although this was not observed in tests with aquatic invertebrates (Dixon and Prosser 1986). Studies with isolated rat hepatoma cells, TBT, and PCB 126, show that TBT inhibits cytochrome P-4501A activity, and PCB 126 induces EROD activity. However, PCB-induced EROD activity was potentiated by coexposure to low noncytotoxic concentrations of TBT (Kannan et al. 1998b). Authors concluded that TBT does not interfere with Ah receptor binding and that potentiation of EROD activity and cytotoxicity as a result of coexposure to PCB 126 and TBT is significant because they coaccumulated in a variety of marine organisms. 

Kannan, K., D.L. Villeneuve, A.L. Blankenship, and J.P. Giesy. 1998b. Interaction of tributyltin with 3,3, 4,4, 5-pentachlorobiphenyl-induced ethoxyresorufin O-deethylase activity in rat hepatoma cells. Jour. Toxicol. Environ. Health 55A 373-384. 

PCB 126 isolated rat hepatoma cells 49-3140 pM PCB 153 EROD activity increases in dose-dependent manner potentiated by coexposure to low noncytotoxic concentrations of tributyltin 31... 

Tillitt, D.E., J.P. Giesy, and G.T. Ankley. 1991. Characterization of the H4IIE rat hepatoma cell bioassay as a tool for assessing toxic potency of planar halogenated hydrocarbons in environmental samples. Environ. Sci. Technol. 25 87-92. 

Figure 6.2 Ethoxyresorufin-O-deethylase(EROD) induction in H4IIE rat hepatoma cells exposed to an SPMD dialysate. Four Standard SPMDs were deployed for a 28 day period in Bayou Meto, Arkansas. Doses of dialysate were normalized to gram-equivalents of triolein per mg of cellular protein. This figure was generated by Don Tillitt, USGS-CERC, Columbia, MO, USA and is reprinted with permission from the American Petroleum Institute (Huckins et al., 2002).

The concentration of toxin which causes a 50% reduction in cell bound dye after five days in culture. Cell lines used were H4TG, thioguanine-resistant rat hepatoma cells MDCK, Madin-Darb and canine kidney cells NIH3T3,NIH Swiss mouse embryo fibroblasts and KA31T, Kirsten strain of Moloney sarcoma virus-transformed 3T3 cells. 

As yet only a limited number of bilirubin conjugates can be synthesized in vitro. Mono- and diglucuronosides of bilirubin predominate in rat bile (F6, Hll, 03, S6). In accordance with these observations, isolated liver preparations and liver slices from rat (S6), and rat hepatoma cells (R9)... 

DIA, DNA strand breaks, rat hepatoma cell line (Reuber) in vitro - NT 35 Gordon et al. (1985)... 

In vitro, in the absence of an exogenous metabolic system, 2-nitropropane induced unscheduled DNA synthesis in rat and mouse liver cells. It induced gene mutations in Chinese hamster cells and rat hepatoma cells in the absence of an exogenous metabolic system. In the absence of an exogenous metabolic system, 2-nitropropane induced micronuclei in three rat hepatoma cell lines but not in Chinese hamster cells. 

GIA, Gene mutation, rat hepatoma H4IIEC3/G eells, hprt loeus in vitro NT 89 Roseher et al. (1990) ... 

MIA, Mieronueleus test, H4IIEC3/G rat hepatoma eell line in vitro NT 267 Roseher et al. (1990) o... 

Genotoxicity studies with A-hydroxyacetamide, a possible metabolite of acetamide, have shown that this agent is weakly mutagenic in Salmonella typhimurium and induces DNA damage in a rat hepatoma cell line. However, it did not bind covalently to DNA in vitro and did not induce morphological transformation of Syrian hamster embryo cells in vitro or inhibit gap-junctional intercellular communication in Chinese hamster lung V79 cells. 

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