Induction of morphological differentiation in cultured mouse neuroblastoma cells by alkylating agents

A series of N-alkyl-N-nitrosoureas, which produce both alkylation and carbamoylation, was found to induce neurite formation in mouse neuroblastoma N-18 cells just as does N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Related compounds, which produce only carbamoylation or nitroguanidination, did not induce morphological differentiation, while methyl methanesulfonate (MMS) and dimethyl sulfate, which produce only alkylation, did. MNNG, methyl nitrosourea and MMS were more effective in the induction of differentiation than their corresponding ethyl derivatives. These data suggested that alkylation contributed to the induction of morphological differentiation in N-18 cells.