title: Ascorbic acid and dietary polyphenol combinations protect against genotoxic damage induced in mice by endogenous nitrosation.
abstract: We investigated whether combinations of ascorbic acid (AA) plus dietary polyphenols can protect in vivo against genotoxic damage induced by endogenous nitrosation. A nitrosation reaction mixture consisting of methylurea (MU) plus sodium nitrite (SN), which can react to form N-nitroso-N-methylurea in the stomach, was administered orally to mice, together with AA and one of the dietary polyphenols ferulic acid (FA), gallic acid (GA), chlorogenic acid (CA), or epigallocatechin gallate (EGCG). Genotoxic damage in bone marrow cells was assessed by measuring micronucleated polychromatic erythrocytes (Mn PCEs) and metaphase chromosome aberrations. When compared to damage induced by MU plus SN alone, co-administration with AA, FA, GA, CA, or EGCG resulted in significant protective effects. Combinations of AA plus EGCG or AA plus CA showed a further protective effect. Reduction in the frequency of Mn PCEs to the control level was obtained following co-administration of a combination of AA, FA, GA, and CA with MU plus SN. A similar trend was observed for metaphase chromosome aberrations. Co-administration of AA, FA, GA, or CA with N-nitroso-N-methylurea (MNU) did not show any significant reduction in genotoxicity, indicating the absence of a protective effect against a preformed N-nitroso compound. Our work demonstrates the protective effects of the 'antinitrosating' combination of AA and dietary polyphenols FA, GA, or CA against genotoxic damage induced by an endogenously formed N-nitroso compound.
authors: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: skabraham44@yahoo.co.in.
authors: Suresh K
authors: SK
authors: Abraham
authors: Nidhi
authors: N
authors: Khandelwal
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002869:Chromosome Aberrations / Q000187:drug effects*; D004249:DNA Damage; D019587:Dietary Supplements; D004900:Erythroblasts / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective; D015538:Nitrosation / Q000187:drug effects; D009603:Nitroso Compounds / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D009603:Nitroso Compounds; D059808:Polyphenols; D001205:Ascorbic Acid
keywords: 2,2,diphenyl-1-picrylhydrazyl; AA; Ascorbic acid; CA; Chromosome aberration; DPPH; EGCG; Endogenous nitrosation; FA; GA; MNU; MU; Micronucleus test; MnPCEs; N-nitroso compound precursors; N-nitroso compounds; N-nitroso-N-methylurea; NCOPs; NOCs; PCEs; Polyphenol; SN; ascorbic acid; chlorogenic acid; epigallocatechin gallate; ferulic acid; gallic acid; methyl urea; micronucleated polychromatic erythrocytes; polychromatic erythrocytes; sodium nitrite