title: Effect of methotrexate on the cell cycle of L1210 leukemia.
abstract: The influence of methotrexate (MTX) on the proliferative activity of cells in different phases of cell cycle has been studied. MTX (5 mg/kg) was injected i.p. 3 days after the inoculation of 5 X 10(6) leukemia cells, into F1 (DBA X C57 BL) mice. It was shown that MTX causes degeneration of cells, being in G1- as well as in S-phase at the time of drug injection. Incorporation of 3H-TdR was suppressed for a period ranging from 2 to 12 hr after MTX administration, which is demonstrated by the decrease in the number of grains per cell. The number of cells labeled after 3H-TdR injection was also sharply decreased during this period. For a period of 3 until 15 hr after MTX administration the mitotic index decreased significantly as a result of inhibition of DNA synthesis. The blocking of the G1-S transition was evident during 4 hr after MTX. Thereafter the G1-S transition proceeds at a rate which is practically equal to that for nontreated controls. MTX did not inhibit transition to mitosis of cells being in G2-phase and in a very late S-phase at the time of drug injection. The sensitivity of G1-cells to the cytocidal effect of MTX shows that for L1210 leukemia cells MTX can be classified as a cycle-specific drug killing both G1-and S-cells rather than S-phase specific agent with self-limitation.
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D007939:Leukemia L1210 / Q000378:metabolism / Q000473:pathology*; D008727:Methotrexate / Q000494:pharmacology*; D008940:Mitotic Index / Q000187:drug effects; D013936:Thymidine / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D013936:Thymidine; D008727:Methotrexate