The Inhibitory Effect Of Grape Procyanidin On The Mutagenicity Of N-nitroso Compounds

Objective To study the inhibitory effect of grape procyanidin (GPC) on the mutagenicity of N-nitroso Compounds by detecting mutant P53 protein, tumor necrosis factor a (TNF-a ) mRNA, poly(ADP-ribose)polymerase (PARP) mRNA after rats were given NaN02 and different dose GPC through mouths. Methods 75 Wistar rats were divided randomly into 5 experimental groups: normal-control led group , positive-controlled group, high dose GPC-treated group, low dose GPC-treated group and vitamin C (VC) -controlled group. Rats in different groups were given NaNO2 through mouths by 50mg/kg to induce mutation. Rats in the high dose and low dose GPC-treated groups were given GPC by 1OOmg/kg and 10mg/kg respectively at the same time, and those of in the vitamin C-controlled group were given VC by lOOmg/kg. Rats in normal-controlled group weren' t given NaNO2 but normally fed. After eight weeks, the changes of liver histology were investigated by means of HE staining, and immunohistochemistry method and in situ hybridization were applied to measure the expression level of mutant P53 protein, TGF-B 1mRNA , TNF-a mRNA and PARPmRNA of hepatocytes and bone marrow micronucleus rates were measured in different groups. Results The rates of positivecells of TGF-B 1mRNA, TNF-a mRNA and PARPmRNA in the high dose and low dose GPC-treated groups were 6. 96 %, 11. 94 %, 11. 48 % and 14. 03 %, 18.16 %, 21. 25% respectively. The differences between the two groups had statistical significance (P<0. 05). The rates of positive cells of the two GPC groups were higher than those of the normal-controlled group but lower than the positive-controlled group, and the differences between them had statistical significance (P<0. 05). The expression results of the vitamin C- controlled group were between those of the high dose GPC-treated group and low dose GPC-treated group. The expression results of mutant P53 protein and micronucleus rates of bone Marrow in different groups had the same trend as those of TGF-B 1mRNA, TNF- a mRNA and PARPmRNA. Conclusion GPC can inhibit the mutation of P53 gene and the abnormal expressions of TGF-B1mRNA, TNF-a mRNA and PARPmRNA induced by N-nitroso Compounds, and it can decrease the micronucleus rate of bone Marrow, so that it has a remarkable inhibitory effect on the mutagenicity of N-nitroso Compounds.