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

Abstract:

: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. Proteinase-sensitive cross-links form more rapidly than do proteinase-resistant cross-links in cells treated with chloroethylnitrosoureas, perhaps because these agents can chloroethylate protein sulfhydryl or amino groups followed by rapid reaction of these chloroethylated groups with DNA. Although both types of cross-links produced by nitrogen mustard disappeared or were repaired after 24 hr, the removal of cross-links produced by chloroethylnitrosoureas either did not occur or was incomplete in 24 hr. In addition to cross-links, cells treated with haloethylnitrosoureas exhibited DNA strand breaks; a method is suggested for estimating the apparent frequencies of strand breaks and cross-links in the DNA.

journal_name

Cancer Res

journal_title

Cancer research

authors

Ewig RA,Kohn KW

subject

Has Abstract

pub_date

1978-10-01 00:00:00

pages

3197-203

issue

10

eissn

0008-5472

issn

1538-7445

journal_volume

38

pub_type

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