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The base sequence selectivity for reaction at the guanine- position was examined for a series of structurally related triazenes by a modification of a standard DNA sequencing method. The monomethyl and monochloroethyl triazenes alkylate guanines extensively at the position with a general preference for runs of contiguous guanines, similar to, but not as striking as that observed previously for the chloroethylnitrosoureas. In contrast to the nitrosoureas, the triazenes had patterns of base sequence selectivity that differed somewhat from agent to agent, with the monochloroethylphenyltriazene having the pattern most different from the others in the series. Thus, the nature of the nonalkylating portion of the molecule can influence the ultimate alkylation preference. The monoethylating analogues alkylated weakly with little sequence preference, and the dlinethyl analogues were essentially unreactive in this system. [ABSTRACT FROM PUBLISHER]

A series of alkyltriazenylimidazoles have been investigated for their differential cytotoxicity towards the HT-29 (Mer) and BE (Mer) cell lines and for their ability to cause DNA strand breaks and cross-links. A monomethyltriazene, and some hydroxymethyltriazene derivatives capable of generating the monomethyltriazene , were preferentially cytotoxic towards the BE cell line compared with the HT-29 cell line, with very close similarity in the differential toxicity to the analogous monochloroethyltriazene. In contrast, the dimethyl-and monoethyltriazenes in the series display reduced toxicity towards the BE cell line with little or no differential toxicity between BE and HT-29 cell lines. With another pair of human cell lines, the IMR-90 (Mer and VA-13 (Mer) cells, the monomethyl- and monochloroethyltriazenes were again more cytotoxic to the Mer− cells. Neither the formation of DNA single-strand breaks or DNA-protein cross-links could account for the differential cytotoxicity oberved in the Mer and Mer cells. More importantly, the inability of the monofunctional monomethyltriazene to cross-link DNA tends to question the role of DNA inter-strand cross-linking as a mechanism for cell killing by chloroethylating agents. [ABSTRACT FROM PUBLISHER]