COMPARATIVE-EVALUATION OF CYTOTOXICITY AND METABOLISM OF 4 ALDEHYDES IN 2 HEPATOMA-CELL LINES

The metabolism of acetaldehyde (ACA), benzaldehyde propionaldehyde (PA ) and valeraldehyde (VA) has been studied in two hepatoma cell lines, the rat HTC and mouse Hepa 1c1c7 cells. The cytotoxicity of the four a ldehydes to these two cell lines has been compared. The end-points for evaluating cytotoxicity were 1) total macromolecular content (TMC) of confluent cultures, and 2) colony forming ability of dividing cells. These two assay systems had different sensitivities for the toxicity o f aldehydes, probably due to different numbers of target cells. The ac tivities of aldehyde dehydrogenases (NAD- and NADP-dependent, ALDH), a lcohol dehydrogenase and aldehyde reductase were markedly greater in t he HTC cell line compared to the Hepa 1c1c7 cell line, especially with BA as substrate. The cytotoxicities of aldehydes were generally stron ger in the HTC cell line than in the Hepa 1c1c7 cell line, with the CF test. Particularly, BA was highly toxic to the HTC cells, which posse ssed the highest ALDH levels. Moreover, the treatment with (diethylami no)benzaldehyde, an AI;DH inhibitor, completely abolished the toxicity of BA. Taken together, all these findings suggest that several cell l ines expressing different aldehyde metabolizing activities could be us ed especially in the prescreening phase to distinguish the metabolism- dependent cytotoxic effects from the metabolism independent effects.