DNA strand scission and cross-linking by diaziridinylbenzoquinone (diaziquone) in human cells and relation to cell killing.

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.

Interstrand DNA crosslinking by 4,5'8-trimethylpsoralen plus monochromatic ultraviolet light. Studies by alkaline elution in mouse L1210 leukemia cells.

DNA crosslinking by 4,5',8-trimethylpsoralen plus monochromatic ultraviolet light of wavelength 365 nm was studied in mouse L1210 leukemia cells. DNA breaks and crosslinking were evaluated by alkaline elution of DNA from poly(vinyl chloride) filters. Trimethylpsoralen plus 365 nm light produced DNA crosslinks but not breaks.

DNA crosslinking and cytotoxicity in normal and transformed human cells treated with antitumor nitrosoureas.

Normal (IMR-90) and simian virus 40-transformed (VA-13) human embryo cells were treated with antitumor nitrosoureas, and the effects on cell viability and cell DNA were compared. All six nitrosoureas tested were more toxic to VA-13 cells than to IMR-90 cells as measured by decrease in cell proliferation or in colony formation. The nitrosoureas capable of generating alkylisocyanates produced a smaller difference between the cell types than did derivatives lacking this capacity.

DNA-protein crosslinking by trans-platinum(II)diamminedichloride in mammalian cells, a new method of analysis.

DNA-protien crosslinks produced in mouse leukemia L1210 cells by trans-Pt(II)diamminedichloride were quantitated using the technique of DNA alkaline elution. DNA single-strand segments that were or were not linked to protein were separable into distinct components by alkaline elution after exposure of the cells to 2--15 kR of X-ray. Protein-linked DNA strands were separated on the basis of their retention of filters at pH 12 while free DNA strands of the size generated by 2--15 kR of X-ray passed rapidly through the filters.

DNA-protein cross-linking and DNA interstrand cross-linking by haloethylnitrosoureas in L1210 cells.

Bifunctional alkylating agents are known to produce cross-links between DNA and protein and between paired DNA strands. The possibility of discriminating these two classes of cross-links in L1210 cells treated with haloethylnitrosoureas or nitrogen mustard was explored with the alkaline elution technique. Two classes of cross-links were demonstrated, based on sensitivity to proteinase K; the proteinase-sensitive cross-links appear to be DNA-protein cross-links, and the proteinase-resistant class may include interstrand cross-links.