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


CONCLUSIONS
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.
Laboratory of Animal Breeding and Experimental Research Center, Faculty of Medicine, Gazi University, Ankara, Turkey. neslihan.gurbuz@gazi.edu.tr
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Gurbuz
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Ozkul
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Burgaz
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000633:toxicity*; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology*
D018906:Antineoplastic Agents, Alkylating; D000975:Antioxidants; D003520:Cyclophosphamide; D001205:Ascorbic Acid; D000111:Acetylcysteine