Mechanism of action of the nitrosoureas--V. Formation of O6-(2-fluoroethyl)guanine and its probable role in the crosslinking of deoxyribonucleic acid.

Abstract:

:DNA which has been exposed to 2-haloethylnitrosoureas has been shown to contain the chemical crosslink 1-(N3-deoxycytidyl), 2-(N1-deoxyguanosinyl)-ethane [W. P. Tong, M. C. Kirk and D. B. Ludlum, Cancer Res. 43, 3102 (1982)]. We have hypothesized that this structure is formed by an initial attack of a 2-haloethyl group on the 6 position of guanine followed by an intramolecular rearrangement and secondary crosslinking reaction with cytosine. We have now shown that DNA which had been reacted with N-(2-fluoroethyl)-N'-cyclohexyl-N-nitrosourea contained O6-(2-fluoroethyl)guanine and have thus demonstrated that the first step in the proposed mechanism occurs. Furthermore, O6-(2-fluoroethyl)guanosine hydrolyzed to N1-(2-hydroxyethyl)guanosine, showing that the necessary intramolecular rearrangement occurs. These two observations greatly strengthen the proposed route to DNA crosslinking by the 2-haloethylnitrosoureas.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Tong WP,Kirk MC,Ludlum DB

doi

10.1016/0006-2952(83)90420-3

subject

Has Abstract

pub_date

1983-07-01 00:00:00

pages

2011-5

issue

13

eissn

0006-2952

issn

1873-2968

pii

0006-2952(83)90420-3

journal_volume

32

pub_type

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