In vitro DNA deamination by alpha-nitrosaminoaldehydes determined by GC/MS-SIM quantitation.

Abstract:

:The deamination of DNA bases by three alpha-nitrosaminoaldehydes, butylethanalnitrosamine, methylethanalnitrosamine, and N-nitroso-2-hydroxymorpholine (NHMOR), the direct metabolite of potent animal carcinogen N-nitrosodiethanolamine, was demonstrated by a set of in vitro experiments. The deamination of guanine, adenine, and cytosine bases in nucleotides, oligonucleotides, and calf thymus DNA gave xanthine, hypoxanthine, and uracil, respectively. The order of relative reactivities of the bases was as listed above. Deamination of cytosine to uracil was detected by the reaction of (32)P-labeled oligonucleotide ([5'-(32)P]CGAT) followed by enzymatic hydrolysis. Quantitative analysis of deamination of guanine and adenine in calf thymus DNA was performed by a gas chromatography/mass spectrometry-selected ion monitoring method. Both the extent and the rate of the deamination reactions which occur by transnitrosation from the alpha-nitrosaminoaldehyde to the base were determined for formation of xanthine and hypoxanthine. The deamination of guanine by NHMOR remained significant at low substrate levels.

journal_name

Chem Res Toxicol

authors

Park M,Loeppky RN

doi

10.1021/tx990126d

subject

Has Abstract

pub_date

2000-02-01 00:00:00

pages

72-81

issue

2

eissn

0893-228X

issn

1520-5010

pii

tx990126d

journal_volume

13

pub_type

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