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Gu S, Wu Y, Yang J. (2015) Screening of cytoprotectors against methotrexate-induced cytogenotoxicity from bioactive phytochemicals, by umu test combined with micronucleus Assay. PeerJ PrePrints3:e1579https://doi.org/10.7287/peerj.preprints.1286v1
To develop new cytoprotectors to reduce the risk of second cancers caused by methotrexate-induced cytogenotoxicity, cytoprotective effects of ten kinds of phytochemicals and their combinations were evaluated by umu test combined with micronucleus assay. It is demonstrated that allicin, proanthocyanidins, polyphenols, eleutherosides and isoflavones owned higher antimutagenic activities than other phytochemicals. At the highest dose tested, the MTX genetoxicity was inhibited by 34.03%~67.12%. Of all the bioactive phytochemical combinations, the combination of grape seed proanthocyanidins and eleutherosides from siberian ginseng as well as green tea polyphenols and eleutherosides showed stronger antimutagenic effects, the inhibition rate of methotrexate-induced genotoxicity separately reached 74.7 ± 6.5 % and 71.8 ± 4.7%. The Kunming mice treated by MTX along with bioactive phytochemicals combinations showed significant reduction in micronucleus induction and sperm abnormality rate compared to MTX treated control groups without cytoprotector candidates (p<0.01). Moreover, obvious increases in thymus and spleen indices were observed in cytoprotector candidates treated groups. The results indicated that bioactive phytochemicals combinations owned potentials to be used as new cytoprotectors, besides umu test was the same effective assay to evaluate antimutagenic potential of phytochemicals as Ames test.
Methotrexate (MTX) is one of the most intensively investigated and effective chemotherapeutic agents. However, a present study has confirmed that MTX induced cytotoxic and genotoxic effects in the germ cells. Furthermore, MTX chemotherapy for gestational trophoblastic tumors and acute lymphoblastic leukemia really increases the risk of second tumors. In this work, we explored an effective and quick method for screening potential antimutagens in bioactive phytochemicals based on umu assay coupled with micronucleus test. The results indicated that bioactive phytochemical combinations (grape seed proanthocyanidins and eleutherosides from siberian ginseng as well as green tea polyphenols and siberian ginseng extract) could be used as new cytoprotectors, besides umu test was the same effective assay to evaluate antimutagenic potential of phytochemicals as Ames test.
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