Kalpana Agarwal

MODIFYING ROLE OF PHYLLANTHUS EMBLICA AND ASCORBIC ACID AGAINST NICKEL CLASTOGENICITY IN MICE

Nickel, a major environmental pollutant is known for its clastogenic and carcinogenic potential. Dietary inhibitors of mutagenesis and carcinogenesis are of particular importance since they may have a role in cancer prevention. In the present investigation, aqueous extract of edible dried fruits of Phyllanthus emblica, a well known medicinal plant, was fed to Mus musculus for seven consecutive days prior to treatment with different doses of nickel chloride (10, 20 and 40 mg/kg body wt.); the fruit extract significantly reduced the frequency of CA/cell, the percentage of aberrant cells and the frequency of micronuclei induced by all doses of nickel in the bone marrow cells of mice. Ascorbic acid, a major constituent of the fruit, fed for 7 consecutive days in equivalent concentration as that present in the fruit, however, could only alleviate the cytotoxic effects induced by low doses of nickel; at the higher doses it was ineffective. The greater efficacy of the fruit extract could be due to the interaction of its various natural components rather than to any single constituent. The study assumes importance in view of the widespread human exposure to nickel compounds.

Clastogenic effects of copper sulphate on the bone marrow chromosomes of mice in vivo

Copper sulphate administered intraperitoneally to Swiss albino mice in vivo induced a significant increase in the frequency of chromosomal aberrations in bone marrow cells as all concentrations used (1.1-6.6 mg/kg b.w.), when compared to the negative control. Statistical analysis indicates that the degree of clastogenicity was directly related to the concentrations used and indirectly to the period of exposure. The effect was maximal at 6 h after treatment as compared with 12 and 24 h.

Ciprofloxacin: mammalian DNA topoisomerase type II poison in vivo

Ciprofloxacin (CF), a fluoroquinolone widely used as a potent antimicrobial drug, was evaluated in vivo in mouse bone marrow cells for its ability to induce clastogenicity and DNA damage in terms of increased sister-chromatid exchange (SCE) frequencies. Doses of 0.6, 6 and 20 mg/kg body weight of CF given intraperitoneally induced a positive dose-dependent significant clastogenicity (trend test alpha < or = 0.05), though the effects were not specific for specific phases of the cell cycle. The DNA-damaging effect observed as increased SCE frequencies using doses of 0.15, 0.30, 0.60, 1.2 and 6 mg/kg body weight showed a significant dose-dependent increase (trend test alpha < or = 0.05; lowest effective concentration 1.2 mg/kg of body weight). Compared to a potent eukaryotic DNA topoisomerase type II poison, etoposide (VP-16, 0.5, 1 and 5 mg/kg body weight, given intraperitoneally), ciprofloxacin produced comparable dose-dependent SCE frequency increases. Ciprofloxacin was postulated to be specific for the target DNA gyrase, the prokaryotic homologue of DNA topoisomerase type II enzyme. The present paper along with the existing earlier data strongly suggest that topoisomerase type II and DNA gyrase are physiological targets for the drug action. In view of the present significant in vivo mammalian DNA topoisomerase type II-mediated genotoxicity and clastogenicity data, ciprofloxacin should be administered with caution.

Phenethyl isotiocyanate modulates clastogenicity of mitomycin C and cyclophosphamide in vivo

Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables, is an effective chemopreventive agent against N-nitrosamine-induced carcinogenesis. We have investigated the extent to which PEITC modulates the clastogenicity of standard genotoxicants, mitomycin C and cyclophosphamide, using bone marrow cells of Swiss albino mice. PEITC, 1 mumol/kg body weight in corn oil was administered by gavage for 7 consecutive days to prime the animals. 24 h later, mice received a single dose of cyclophosphamide (10 or 20 mg/kg body weight) or mitomycin C (1 or 2 mg/kg body weight) intraperitoneally. Clastogenicity of the chemicals was compared using PEITC-primed and non-primed animals 24 h after clastogen treatment. As a single agent, PEITC is not clastogenic even after 7 days of priming. Oral priming with PEITC decreased the aberrations per cell values by 22-67% in all cases. PEITC could only alleviate the clastogenicity of 1 mg/kg body weight mitomycin C to near-control values (p < or = 0.05). Although PEITC is reported to be effective against N-nitrosamine-induced tumorigenesis by preventing metabolic activation and by blocking the reactive species formed, it is virtually ineffective against the clastogenicity of cyclophosphamide. The results of inhibition by PEITC of the clastogenicity of mitomycin C suggest that the modulation of mitomycin C bio-activation contributes to, but may not be sufficient for, PEITC chemoprevention of clastogenicity by mitomycin C.

In vivo cytogenetic studies on mice exposed to natural food colourings.

Safflower Yellow and Kokum Red, two food colourings developed from natural plant products, were assessed in vivo for their clastogenic potential. Swiss albino male mice were exposed to the compounds through ip injections. Bone marrow cells isolated from femora were analysed for chromosome aberrations. The results show that the two food colourings were weakly clastogenic.

Genotoxicity studies of the food additive ester gum

Ester gum (EG) is used in citrus oil-based beverage flavourings as a weighting or colouring agent. In the present study, concentrations of 50, 100 and 150 mg/kg body weight were administered orally to male Swiss albino mice, and sister chromatid exchange and chromosomal aberration were used as the cytogenetic endpoints to determine the genotoxic and clastogenic potential of the food additive. Although EG was weakly clastogenic and could induce a marginal increase in sister chromatid exchange frequencies, it was not a potential health hazard at the doses tested.

Potentiation by caffeine of the frequencies of chromosomal aberrations induced by chronic exposure to fenfluramine in mice

Fenfluramine (Fen), an amphetamine-derivative widely used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice for assessing its clastogenic potentials. Concentrations of 0.75, 1.50 and 5.0 mg Fen/kg body weight (b.w.) were administered orally for the study. Long-term treatment for 21 days showed dose-dependent significant increase in chromosomal aberrations on the 8th day. A significant decrease in aberration levels was seen in the late treatment period. Caffeine alone produced dose- and duration-dependent clastogenicity at doses of 2.0, 4.0 and 6.0 mg/kg b.w. when given by gavage. Using caffeine post-treatment (4.0 and 6.0 mg/kg b.w.) 2 h after Fen application, a strong synergism could be seen in the late treatment period as shown by the dose-response curves and by statistical analysis using the principle of least squares. The results support the hypothesis that prolonged Fen application induces dose-dependent increase in post-replication repair and caffeine enhanced toxicity by inhibiting repair process(es). The study suggests that Fen is a clastogen and since caffeine may have a synergistic effect, it should be avoided during treatment.