Melatonin prevents delta-aminolevulinic acid-induced oxidative DNA damage in the presence of Fe2+.
Delta-aminolevulinic acid (ALA), a heme precursor which accumulates during lead poisoning and acute intermittent porphyria, is reported to cause liver cancer. The carcinogenic mechanisms of ALA may relate to its ability to generate free radicals through metal-catalyzed oxidation which cause oxidative DNA damage. The aim of this study was to compare the efficacy of melatonin, trolox (vitamin E) and mannitol in altering DNA damage induced by ALA. Herein, we found, in the presence of Fe2+, that ALA-induced formation of 8-hydroxydeoxyguanosine in calf thymus DNA was dose and time-dependent. Melatonin, mannitol and trolox, all of which are free radical scavengers, inhibited the formation of 8-hydroxydeoxyguanosine in a concentration-dependent manner. The concentration of each (melatonin, mannitol and trolox) required to reduce DNA damage by 50%, i.e., the IC50, was 0.52, 0.84 and 0.90 mM, respectively.
Qi
W
W
Department of Cellular and Structural Biology, The University of Texas Health Science Center San Antonio, 78229-3900, USA.
Reiter
R J
RJ
Tan
D X
DX
Manchester
L C
LC
Calvo
J R
JR
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000622:Aminolevulinic Acid / Q000037:antagonists & inhibitors*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002417:Cattle; D002839:Chromans / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008353:Mannitol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008550:Melatonin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D013950:Thymus Gland / Q000737:chemistry; D013997:Time Factors
D000975:Antioxidants; D002839:Chromans; D008353:Mannitol; D000622:Aminolevulinic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D008550:Melatonin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid