IRON ENHANCEMENT OF OXIDATIVE DNA DAMAGE AND NEURONAL CELL DEATH INDUCED BY SALSOLINOL

Author: Surh Young-Joon   Jung Youn-Joo   Jang Jung-Hee   Lee Jeong-Sang   Yoon Hye-Ran  

Publisher: Taylor & Francis Ltd

ISSN: 1087-2620

Source: Journal of Toxicology and Environmental Health, Vol.65, Iss.5-6, 2002-03, pp. : 473-488

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Abstract

A group of naturally occurring isoquinoline alkaloids have been detected in certain regions of mammalian brain. One such compound is salsolinol (SAL; 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline). This endogenous isoquinoline derivative has been considered to be implicated in the pathophysiology of chronic alcoholism and Parkinsonism. The present study deals with the DNA strand scission induced by SAL in the presence of iron. Incubation of &phis;X174 DNA with SAL and ferric ion led to conversion of the supercoiled DNA to open circular and linear forms, which was inhibited by the iron chelator deferoxamine, catalase, and scavengers of reactive oxygen species. SAL in combination with Fe(III) also produced 8-hydroxydeoxyguanosine in calf thymus DNA. Exposure of PC12 cells to SAL produced concentration-dependent reduction in viability, which was exacerbated by iron and ameliorated by deferoxamine.