Epigenetic effects of the methylating agent 5-(3-methyl-1-triazeno) imidazole-4-carboxamide in human melanoma cells.

The anti-tumour methylating agent 5-(3-methyl-1-triazeno) imidazole-4-carboxamide (MTIC) increased the thymidine and deoxycytidine pools but not the deoxyguanosine pool in human melanoma cells. Incorporation of deoxyguanosine and deoxyadenosine was strongly inhibited by MTIC due to formation of the decomposition product 5-aminoimidazole-4-carboxamide (AIC). Theophylline, natural nucleosides and sulphydryl compounds did not affect the toxicity of MTIC in either MTIC-sensitive (Mer-) or autologous-resistant (Mer+) melanoma cells. 3-Aminobenzamide (3 mM for 48 h), an inhibitor of ADP-ribosyl transferase, greatly enhanced MTIC toxicity in the resistant compared with the sensitive cell line.