Biochemical and cytotoxic actions of 3,6-dihydroxy-4,5-dimethylphthalaldehyde in sarcoma 180 cells

The replication of Sarcoma 180 cells in culture was inhibited by 3,6-dihydroxy-4,5-dimethylphthalaldehyde (HMPA). The inhibition of growth caused by HMPA was evident after treatment of cells with drug for only 15 min. This exposure period caused decreased in (a) cloning efficiency, (b) transport and/or phosphorylation of [3H]thymidine and [3H]uridine, (c) incorporation of radioactive nucleosides into acid-insoluble material, and (d) incorporation of [3H]leucine into protein. Examination of the cytotoxicities of the model compounds 2,3,5,6-tetramethyl-1,4-dihydroquinone (durohydroquinone) and o-phthalaldehyde indicated that the dialdehyde portion of the molecule was responsible for the cytocidal effects of HMPA. The ratio of adenosine triphosphate to adenosine diphosphate in the acid-soluble fraction of Sarcoma 180 cells incubated in vitro with HMPA for 45 min was reduced in a concentration-dependent manner. The reduction in the ATP pool size produced by HMPA contrasts with the action of the periodate oxidation product of cytidine dialdehyde, which has been reported to increase the intracellular concentration of adenosine triphosphate.