The effects of 3,6-diaziridinyl-2,5-bis(carboethoxyamino)-1,4-benzoquinone (diaziquone; AZQ) on various cell types were studied in relation to two chemical reactivities that this drug would be expected to have intracellularly. AZQ can undergo a reduction-oxidation cycle of the quinone function; this could generate free radicals which could produce DNA damage, especially DNA strand scission. The second reactivity, based on the two aziridine groups, could produce alkylation reactions that could produce DNA cross-links. DNA strand breakage and cross-linking were measured by alkaline elution and were compared with cell killing assayed by colony survival. Among the cell strains studied (human IMR-90, VA-13, and HT-29 and mouse L1210), marked differences were found in the magnitudes of DNA strand breakage and interstrand cross-linking produced by AZQ. Most striking, IMR-90 cells exhibited substantial strand breakage and little or no interstrand cross-linking, whereas the reverse was true for HT-29 cells. Cell killing correlated well with interstrand cross-linking but did not correlate with strand scission in these cell lines. It is concluded that AZQ produces DNA strand breaks and interstrand cross-links by different mechanisms which vary independently among different cell lines.

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