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.
Gurbuz
N
N
Laboratory of Animal Breeding and Experimental Research Center, Faculty of Medicine, Gazi University, Ankara, Turkey. neslihan.gurbuz@gazi.edu.tr
Ozkul
A
A
Burgaz
S
S
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