leucovorin rescue

[rowancv]

if anyone can help..

from what i understand, methotrexate inhibits thylimidate synthase, so the cell can't make dUMP, thus not being able to make RNA, thus DNA, and thus stopping the replication cycle of the tumor cell (ie. tumor cells die). but this will affect normal cells at a high dose, so they use leucovorin to "rescue" the normal cells. QUESTION (assuming what i've learned is correct, if not, please correct me): how is leucovorin able to rescue only host cells and NOT cancer/tumor cells? does it physically remove methotrexate form receptors? i've read that it can enter only host cells and not cancer cells.

can anyone clarify this and/or maybe post a good link/journal article that will be able to explain this? thanks!!

- rowan
rowancv@yahoo.com

[bpoichan]

i believe that the tumor cells wont be rescued...
the leucovorin rescue is used when DIHYDROFOLATE needs to be converted to TETRAHYDROFOLATE by the enzyme Dihyodrofolate reductase...
methotrexate has an inhibitory action on DHF reductase

inhibiting dihydrofolate conversion to tetrahydrofolate would deplete the tetrahydrofolate pool, hence decreasing methylene FH4 and decrease DNA production..

methotrexate inhibits DHF reductase.. i dont remember reading that it inhibited thymidilate synthase..

so all that will happen with the leucovorin rescue and also the Formiminoglutamic acid as well, is that it will replete the system with methylene Tetrahydrofolate so that the RNA...DNA synthesis wont be affected..

hope i was clear.. it 5 am here!