Methanolic extracts (mg mL -1 ) of Dicoma anomala (0.0625, 0.125, 0.25), Chenopodium album (0.078, 0.156, 0.313), used in traditional medicine in Lesotho, and Camellia sinensis (0.1094, 0.2085, 0.44) were assessed for cytotoxicity, genotoxicity and modulation of Cyclophosphamide (CP 1.25 mg mL -1 ) -and EMS (0.25 mg mL -1 )-induced genotoxicity using the Allium cepa assay following 24 hours treatment. Cytotoxicity was measured by the mitotic index (MI). Genotoxicity (GT) was expressed as the number of aberrant mitotic cells per 100 mitotic cells. The MI and GT of test groups (triplicates), were compared with the negative (water) control group using t-test. Modulatory effect (ME) was calculated as, ME(%) = (1-(A-B)/(A-C) × 100) -1. A positive ME indicated an increase (synergism or potentiation) while a negative ME indicated a reduction (anti-genotoxicity) of mutagen-induced genotoxicity. The concentrations of D. anomala extract were cytotoxic and genotoxic. Mixtures of CP or EMS with the lower concentrations of D. anomala extract were more genotoxic than CP (250.50% increase) or EMS (149.74 and 157.37 % increase) or extracts alone. Only 0.313 mg mL -1 of C. album extract was cytotoxic but none of the three concentrations was genotoxic. Mixtures of CP with extracts of C.album were cytotoxic. CP-induced genotoxicity was reduced (55.18, 68.36, 57.40 %) and EMS-induced genotoxicity was also reduced by low concentrations (50.72, 61.13 %) of C.album extract. However, 0.313 mg mL -1 C. album extract increased (236.75%) EMS-induced genotoxicity. C. sinensis extracts and their mixtures with CP were not cytotoxic or genotoxic. CP-induced genotoxicity was reduced (63.61, 66.62, 78.64 %) but EMS-induced genotoxicity was increased (124.97, 4.48, 110.52 %) by C. sinensis extract.
In order to study how two chemicals interact to induce micronuclei, simple ethylating agents [ethyl methanesulfonate (EMS), ethyl ethanesulfonate (EES) and N-ethyl-N-nitrosourea (ENU)], spindle poisons [vincristine sulfate (VINC) and colchicine (COL)] and an oxidizing agent [potassium bromate (KBrO3)] were used as model chemicals for combination treatments. The frequency of micronucleated reticulocytes (MNRETs) was evaluated in mice treated with two of these chemicals at a time. The combinations of ethylating agents (EMS and EES; EMS and ENU) and of spindle poisons (VINC and COL) induced more micronuclei than those expected on an additive basis. The apparent synergism was due to a 'combined dose' which could be calculated by the dosimetric conversion of one chemical to the other, when damage induced by each chemical was 'equivalent' in the induction of MNRETs. In contrast, no apparent synergism in induction of micronuclei was observed when two chemicals with different modes of clastogenic action (EMS and KBrO3 or EMS and VINC) were combined.
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