Three further triterpenoid saponins from Gleditsia caspica fruits and protective effect of the total saponin fraction on cyclophosphamide-induced genotoxicity in mice.

Three triterpenoidal saponins were isolated from the saponin fraction derived from a Gleditsia caspica Desf. methanolic fruit extract. The isolated saponins were identified as gleditsiosides B, C, and Q based on spectral data. The saponin-containing fraction was evaluated in vivo for genotoxic and antigenotoxic activities. The fraction caused no DNA damage in Swiss albino male mice treated with a dose of 45 mg/kg body weight for 24 h, although it significantly inhibited the number of chromosomal aberrations induced by cyclophosphamide (CP) in bone marrow and germ cells when applied before or after CP administration. The inhibitory indices in chromosomal aberrations were 59% and 41% for bone marrow and 48% and 43% for germ cells, respectively. In addition, the saponin fraction was found to reduce the viability of the human tumor cell line MCF-7 in a dose-dependent manner with an extrapolated IC50 value in the range of 220 µg/mL.

Genotoxicity of benomyl and its residues in somatic and germ cells of mice fed on treated stored wheat grains.

Swiss mice were fed for 2, 4 and 8 weeks wheat grains treated with 1, 2, and 4 g benomyl/kg and stored for 6 and 12 weeks. The maximum effect of benomyl on the induction of chromosomal aberrations was observed after feeding mice for 8 weeks with wheat grains treated with 4 g benomyl/kg and stored for 12 weeks. Its proportion differed significantly in bone marrow and spermatocyte cells, 15+/-0.51% vs. 13.4+/-0.66%, respectively, from that in nontreated mice (background level), 4.4+/-0.24% and 3.8+/-0.20%, respectively. Lengthening the storage period of treated wheat grains caused a dose-dependent increase in the frequency of sister chromatid exchanges: 8.61+/-0.34 vs. 4.16+/-0.06/cell. The proportion of sperm-head abnormalities increased by lengthening the period of storage and feeding: 7.7+/-0.41% vs. 3.25+/-0.12%. In another experiment mice were orally treated by gavage with benomyl at 50, 100, 150, 200 mg/kg; a significant and dose-dependent increase in sperm-head abnormalities was observed. These findings demonstrate that benomyl (a 50% wettable powder formulation) and its residues in wheat grains are genotoxic in mice.

In vivo antimutagenic effect of vitamins C and E against rifampicin-induced chromosome aberrations in mouse bone-marrow cells.

-The genotoxic effect of rifampicin (RMP), one of the most active antituberculosis agents is studied. Also, the possible protection provided by the natural antioxidant vitamins C (VC) and E (VE) against the genotoxic effect of RMP is assessed. Mice were orally treated by gavage with 10, 50, 150 and 300 mg RMP kg(-1) body weight (bw). Also, oral treatment was conducted with RMP plus the vitamins. Mice received 300 mg RMP kg(-1) bw plus 100, 200 and 400mg VC or VE kg(-1) bw. Samples were taken 24h after the treatment. Repeated treatments with: (1) the therapeutic dose of RMP (10 mg kg(-1) bw); (2) RMP plus a dose of 25, 50 and 75 mg VC kg(-1); (3) RMP plus 10, 20 and 40 mg VE kg(-1) bw for 30 consecutive days were conducted. The tested doses of RMP induced a significant increase in the percentage of chromosome aberrations. However, a lower percentage of chromosome aberrations was observed when animals were treated with the therapeutic dose for 30 consecutive days. The obtained results revealed that chromosome aberrations induced by RMP decreased to a significant extent when mice were treated with RMP plus VC. The repeated doses of VC reduced the percentage of chromosome aberrations induced by RMP in a significant and dose-dependent manner. On the other hand, repeated doses of VE were not very effective in reducing the percentage of chromosome aberrations induced by RMP. Only the highest dose (3 x 40 mg kg(-1) bw) showed a significant effect (P<0.01). The results on the induction of chromosome damage clearly show that only VC appears able to efficiently protect the bone-marrow cells when given together with RMP, while no significant reduction in the yield of chromosome aberrations was observed for VE in combination with the antituberculosis drug.

Cytogenetic studies on the effect of feeding mice with stored wheat grains treated with malathion.

The cytogenetic effect of malathion residues in wheat grains stored for different periods of time (4, 12, 24 weeks) was evaluated in Swiss mice. The studies included: (1) chromosomal aberrations analysis in bone-marrow and spermatocyte cells; (2) chromosomal aberrations and sister chromatid exchange (SCE) analysis in spleen cell culture from mice fed with stored wheat grains. The tested doses were 8.36 (applied dose), 25.08 and 41.80 mg malathion kg(-1) wheat grains. The results demonstrated that the cytogenetic effect induced in different mouse tissues by malathion residues was dose-dependent and increased with increasing of both feeding and storage periods. Feeding mice with wheat grains stored for 4 weeks had a non-significant effect with respect to the induction of chromosomal aberrations or SCEs. Significant chromosome damage and increase of SCEs were observed in mice fed with wheat grains stored for 12 weeks. The maximum effect was recorded in mice fed for 12 weeks with the grains treated with the highest tested dose and stored for 24 weeks. However, mitomycin C i.p.-injected in mice at 1 mg kg(-1) body weight (b.w.) (positive control) induced a higher effect. The percentage of chromosome aberrations reached 13.60+/-0.98, 13.60+/-0.77 and 11.73+/-0.98 (P<0.01) in bone-marrow, cultured spleen cells and spermatocytes, respectively. The significant increase of abnormalities in spermatocytes was seen for univalent formation only, predominantly of the sex chromosomes. The frequency of SCEs was 10.76+/-0.62 per cell (P<0.01) in cultured spleen cells compared with 5.46+/-0.45 per cell for control and 14.66+/-0.54 per cell for the positive control. The obtained results indicate that malathion residues in stored wheat grains have potential genotoxic effect in mice under the conditions tested.