Hepatomas Enzyme induction

Samuels, H. H., and G. M. Tomkins. 1970. The relation of steroid structure to enzyme induction in hepatoma tissue culture cehs. J. Molec. Biol., 52 57. 

The mechanism of action of drug induced hepatocellular tumors is quite similar to epidermal carcinogenesis. There are a series of biochemical changes such as enzyme induction that are parallel in liver and skin. Hyperplastic nodules result from promoter treatment and these nodules regress if the promoting stimulus is removed up to a critical point, after which the nodule is committed to develop into a hepatoma. The preneoplasic nodules contain enzyme altered foci for y-glutamyltranspeptidase, canalicular ATPase, glu-cose-6-phosphatase and iron deficient foci (Pitot et al., 1982). It is not clear whether or not all of the enzyme alTered foci result in hepatomas but they are certainly direct evidence of enhanced clonal growth or cell section and proliferation of presumably initiated cells. The promotional model can be modified by hormonal and dietary factors and this model has potential use for extrapolation to the human population. 

Miller, A.G., Israel, D. and Whitlock, J.P., Jr (1983) Biochemical and genetic analysis of variant mouse hepatoma cells defective in the induction of benzo(a) pyrene-metabolizing enzyme activity. 

Bioassays using induction of the enzymes ethoxyresorufin o-deethylase (EROD) and/or arylhydrocarbon hydroxylase (AHH) in rat hepatoma H-4-IIE cells (Zacharewski et al. 1989) and modified mouse liver cells (Schuman and Hunter 1988) have been developed and tested on water, soil, and fish samples. The... 

A choline deficient (CD) diet has been shown to exert a strong promoting effect on the emergence of foci of enzyme altered hepatocytes and on the induction of hepatomas in rats initiated with a carcinogen. 

Tawfiq, N., Wanigatunga, S., Heaney, R.K., Musk, S.R., Williamson, G. and Fenwick, G.R. 1994. Induction of the anti-carcinogenic enzyme quinone reductase by food extracts using murine hepatoma cells. Fur. J. Cancer Prev. 3 285-292. 

Functional expression, inhibition and induction of cytochrome P450 (CYP) enzymes in human hepatoma HepaRG cells. Toxicol In Vitro 23 748-753... 

Sawyer T, Safe S. 1982. PCB isomers and congeners Induction of aryl hydrocarbon hydroxylase and ethoxyresorufin-o-deethylase enzyme activities in rat hepatoma cells. Toxicol Lett 13 87-94. 

Uda, Y., Price, K. R., Williamson, G., and Rhodes, M. J. (1997) Induction of the anti-carcinogenic marker enzyme, quinone reductase, in murine hepatoma cells in vitro by flavonoids. Cancer Lett. 120, 213-216. 

The interpretations on the controls of two other well-studied enzymes in tissue culture may be mentioned. Nebert and Gelboin [130] using hamster fibroblasts, and the induction by benzanthracene of microsomal aryl hydroxylase, found that the inducer appeared to cause an increase in mRNA synthesis of the hydroxylase even if protein synthesis was blocked by inhibitors it was therefore concluded that the induction occurred at the level of transcription. In contrast, Tomkins et al. [131], using rat hepatoma cells induced with dexamethasone phosphate to form tyrosine-x-KG-amino transferase (TAT), concluded that the inducer acted at the level of translation to antagonize the action of a repressor. This conclusion was based on the fact that, when actinomycin D at the very high concentration of 5 //g/ml was given several hours after the induction, an enhanced synthesis of the enzyme occurred. To... 

A series of withanolides was evaluated by Su and coworkers for their ability to stimulate quinine reductase induction with cultured mouse hepatoma, Hepa lclc7 cells. It was found that philadelphicalactones A (68) and B (69), ixocarpalactones A (11) and B (70), withaphysacarpin (71), 18-hydroxywithanolide D (72) and withanone (73), subtrifloralactones A (74) and F (75), subtrifloralactones K (76) and L (77), and 3/i-hydroxymethylsubtrifloralactone E (78) are effective inducers of quinine reductase enzyme [64, 88-90]. Gu and coworkers also evaluated the significant quinine reductase potential of 2,3-dihydro-3)S-methoxyixocarpalactone A (79), 2,3-dihydro-3j -methoxyixocarpalactone B (80), 2,3-dihydroixocar-palactone-B (81), and 4)S,7)S,20/ -trihydroxy-l-oxo-with a-2,5 diene-22,26-oUde (82) for their ability to induce quinine reductase in Hepa lclc7 cells [23]. 

---