Reverse chemical mutagenesis: identification of 5-hydroxy-2'-deoxycytidine as a principal mutagenic lesion caused by reactive oxygen species (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Reverse chemical mutagenesis: identification of 5-hydroxy-2'-deoxycytidine as a principal mutagenic lesion caused by reactive oxygen species (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 35:A3505 1994. Unique Identifier : AIDSLINE ICDB/95605190
Feig DI; Sowers LC; Loeb LA; Dept. of Pathology, University of Washington, Seattle, WA 98195

Abstract: An evaluation of the role of oxygen reactive species in carcinogenesis has been hindered by the large number of diverse DNA lesions they cause. The traditional approach has been to chemically identify a lesion first in DNA and subsequently to evaluate its mutagenicity. We present a new approach, Reverse Chemical Mutagenesis: a deoxynucleoside triphosphate is treated with a mutagen or carcinogen and a mutagenic alteration is selected prior to determination of chemical structure. To identify lesions which cause C----T transitions (the most common oxygen radical induced mutation), we incubated dCTP with a reactive oxygen generating system, FeSO4, H2O2, and ascorbic acid. The reaction products were separated by reverse phase and ion exchange chromatography and incorporated by HIV reverse transcriptase into a target gene to assess mutagenicity in a biological assay. One of the mutagenic species thus identified was subsequently determined by mass spectrometry to be 5-hydroxy-2'-deoxycytidine triphosphate. It is incorporated efficiently into M-13 DNA and causes C----T transitions in an E coli host at a higher frequency (2.5%) than any previously identified oxidative DNA lesion.

Keywords: Ascorbic Acid/PHARMACOLOGY Deoxycytosine Nucleotides/*PHARMACOLOGY Hydrogen Peroxide/PHARMACOLOGY *Mutagenesis Mutagens/*PHARMACOLOGY Reactive Oxygen Species/*PHARMACOLOGY ABSTRACT
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M9530829

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