Influence of substrate complexity on the diastereoselective formation of spiroiminodihydantoin and guanidinohydantoin from chromate oxidation.

ABSTRACT: Chromate is a human carcinogen with a poorly defined mechanism of DNA damage. In vitro and prokaryotic studies have shown that DNA damage may occur via the formation of the hydantoin lesions guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp) from further oxidation of 8-oxo-7,8-dihydroguanine (8oxoG). The unusual structure of these lesions coupled with their enhanced mutagenicity make them attractive for study with regard to their role in chromate-induced cancer. We have studied the formation of Gh versus Sp and their associated diastereomers following oxidation by model Cr(V) complexes and from in situ chromate reduction by ascorbate and glutathione. Identification of the two optically assigned diastereomers of Sp (R-Sp and S-Sp) as well as the two diastereomers of Gh (Gh1 and Gh2, not

SUBMITTER: Gremaud JN 

PROVIDER: S-EPMC2821960 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature