ELEVATION OF ALDOSE REDUCTASE GENE-EXPRESSION IN RAT PRIMARY HEPATOMAAND HEPATOMA-CELL LINES - IMPLICATION IN DETOXIFICATION OF CYTOTOXIC ALDEHYDES

Aldose reductase and aldehyde reductase are members of the aldo-keto r eductase superfamily, and participate in the reduction of a wide range of carbonyl compounds. We have purified aldose reductase from rat len s and raised antiserum against it in rabbits. Immunoblot analyses usin g this antibody showed that a significant amount of aldose reductase w as expressed in cell lines derived from hepatomas while it was negligi ble in normal hepatocytes. Elevated expression of aldose reductase was also observed in cancerous lesions of 3'-methyl-4-dimethyl-aminoazobe nzene (3'-Me-DAB)-induced hepatocarcinomas. Expression of aldose reduc tase mRNA was confirmed in these cells by Northern-blot analysis, sugg esting that the induction occurred at the stage of gene transcription. The level of aldehyde reductase, however, did not change in cancerous tissue or in the cell lines. The viability of hepatoma cells in the p resence of 8-deoxyglucosone and glyceraldehyde was decreased by an ald ose reductase inhibitor, ONO-2235 -2-methyl-3-phenylpropenylidene]-4-o xo-2-thioxo-3- thiazolidineactic acid). Taken together, induction of a ldose reductase gene expression during hepatocarcinogenesis may render cancer cells resistant to various toxic carbonyl compounds produced d uring metabolism or administered as anti-cancer drugs. (C) 1995 Wiley- Liss, Inc.