INDUCTION OF DNA STRAND BREAKS AND CROSS-LINKS BY 2,5-DIAZIRIDINYL-3,6-BIS(CARBOETHOXYAMINO)-1,4-BENZOQUINONE IN CHINESE-HAMSTER OVARY CELLS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (12) , 5634-5637
Abstract
The DNA-damaging effects pf 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 .mu.M AZQ for 2 h. The single-strand break frequency was 31.3 .+-. 5.3 (SD) 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 .mu.M 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 .mu.M 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 h after drug removal. DNA interstrand cross-links increased within the 1st 6 h of postincubation and then slightly decreased by 12 h and most of the cross-links disappeared after cells were allowed to recover for 24 h. DNA-protein cross-links were immediately formed during the drug treatment period and were gradually decreased after drug removal. [The use of AZQ as an antineoplastic drug was discussed.].