In vitro cytotoxicity of the methylmelamines

Hexamethylmelamine (HMM) and a number of its derivatives are toxic to PC6 plasmacytoma cells in vitro. However, there is no correlation between in vitro cytotoxicity and activity against this tumour in vivo. N-Methylolmelamines are significantly more toxic than HMM itself. These compounds break down to release formaldehyde which is itself a highly cytotoxic agent. Pentamethylmonomethylolmelamine rapidly inhibits the growth of PC6 cells in culture, whereas HMM and pentamethylmelamine (PMM) require prolonged contact with the cells in order to exert a cytotoxic effect. HMM and its metabolites are also toxic to a number of other cell lines. The toxicity of the N-methylols to cultured L1210 leukaemia and Walker 256 ascites cells appears to be due entirely to formaldehyde release, whereas in PC6 cells the methylols appear to be acting more selectively.