Induction of DNA Strand Breaks and Cross-Links by 2,5-Diaziridinyl-3,6-bis(carboethoxyamino)-1,4-benzoquinone in Chinese Hamster Ovary Cells¹

The DNA-damaging effects of 2,5-diaziridinyl-3,6-bis(carboethoxyamino)-1,4-benzoquinone (AZQ) in Chinese hamster ovary cells were investigated. As determined by alkaline elution, DNA strand breaks were observed in cells treated with 50 µm AZQ for 2 hr. The single-strand break frequency was 31.3 ± 5.3 (S.D.) rad equivalents. Strand breaks could also be detected at lower drug concentration if proteinase K treatment was included before DNA elution. In comparison, DNA cross-links were apparent in cells treated with as low as 6.25 µm AZQ. The cross-linking frequencies were 39.7, 124.3, 230.3, and 625.1 rad-equivalents for 6.25, 12.5, 25, and 50 µm AZQ, respectively. Both DNA-DNA and DNA-protein cross-links in AZQ-treated cells were revealed by the proteinase K assay. The DNA strand breaks induced by AZQ were rapidly rejoined within 1 hr after drug removal. DNA interstrand cross-links increased within the first 6 hr of postincubation and then slightly decreased by 12 hr, and most of the cross-links disappeared after cells were allowed to recover for 24 hr. DNA-protein cross-links were immediately formed during the drug treatment period and were gradually decreased after drug removal.