Detection Of DNA Damage Induced By MTX In Multiple Mouse Organs (Liver, Spleen, Bone Marrow, Kidney, Thymus, Testis, Stomach And Peripheral Lymphocytes) Using The SCGE Assay

In order to understand the mechanism of MTX further and to investigate the genotoxic target organs, we studied the DNA damage and the correlation with dose of MTX by using the alkaline single cell gel electrophoresis (comet) assay. Liver, spleen, bone marrow, thymus, kidney, testicle, stomach and peripheral lymphocytes of mice were isolated at lh,3h,6h,12h,24h after 5mg/kg MTX intraperitoneal injection. The results showed that: Significant increase in DNA migration and comet frequency in the spleen, thymus, bone marrow and peripheral lymphocytes were induced after intraperitoneal treatment of MTX at a dose of 1.25~5mg/kg.No obvious increase in DNA single strand breaks was observed in the liver, kidney,testicle and stomach of the mice with the same treatment. The migration of nuclear DNA and comet frequency of spleen, thymus, bone marrow and peripheral lymphocytes in the dose-response study showed a dose-dependent increase. The results indicate that DNA SSBs could be induced by MTX in some cells of mice. There are differences in sensitivity of various organs in the mice and cells of spleen, thymus, bone marrow and peripheral lymphocytes may be the important target cells of MTX. Multiple organ comet assay in vivo is very useful for the evaluation of genotoxicity target organ. The comet tail of peripheral lymphocytes is suitable as a biomarker for reflecting the sensitivity of organs after treatment of MTX.