Effects of vitamin C and N-acetylcysteine against cyclophosphamide-induced genotoxicity in exfoliated bladder cells of mice in vivo.

PURPOSE: To investigate the effects of vitamin C and N-acetylcysteine (NAC) against cyclophosphamide (CP) -induced genotoxic damage in exfoliated bladder cells of mice by micronucleus (MN) assay. METHODS: For each experimental step, 6-8 Swiss albino balb/c male mice were used. CP was used as positive control. Vitamin C (10, 30 and 60 mg/kg) and CP (51.6 mg/kg) were administered intraperitoneally to the experimental animals. Vitamin C was administered twice, one dose 24 h prior to the CP administration and the second dose simultaneously with the CP. NAC (200, 400 and 800 mg/kg) was administered by gavage for 7 consecutive days before the injection of CP. Distilled water and normal saline as negative controls I and II were used, respectively. Ten days after CP treatment, the mice were sacrificed and bladders were isolated and cut, and exfoliated cells were scraped from the bladder walls. Air-dried smears were stained by Feulgen reaction. MN frequencies were scored in 1000 epithelial cells per animal and defined as MN per thousand (per thousand). RESULTS: Three doses of vitamin C (10, 30 and 60 mg/ kg) showed a significant inhibitory effect on MN frequencies in mouse bladder cells when compared with those of positive control group (p <0.05). Dose-dependent inhibitory effect of vitamin C was observed only between the doses of 10 and 60 mg/kg (p <0.05). Histopathological changes that depended on CP- induced inflammatory infiltration and haemorrhage in mucosa propria were not observed in all 3 vitamin C doses. Three doses of NAC (200, 400 and 800 mg/kg) inhibited the CP-induced genotoxicity (p <0.05), however, the antigenotoxic effect of NAC was not dose-dependent. Histopathological changes that depended on CP-induced inflammatory infiltration and haemorrhage in mucosa propria were not observed in 200 and 400 mg/kg NAC dosage. The extent of desquamation in bladder was similar in all 3 doses of NAC when compared with the positive control group. CONCLUSION: Our study indicated that vitamin C and NAC reduced the CP-induced MN frequencies in target (bladder) cells of mice by 41-71% in all cases. The modifying effects of vitamin C and NAC against CP-induced genotoxic damage may be due to their antioxidant, nucleophilic properties and to the ability to act as precursors of glutathione.