[Mechanism of action of anti-cancer drugs from the viewpoint of RNA metabolism].
The mechanism of action of anti-cancer drugs, especially 5-FU, was discussed on the basis of RNA metabolism. After its incorporation into cells, 5-FU is metabolized through the uracil pathway, and finally incorporated into various species of RNA. On the other hand, 5-FU metabolized to FdUMP forms a covalent ternary complex among TS and mTHF, and inhibits de novo TMP synthesis, resulting in the inhibition of DNA synthesis. However, 5-FU was found to exert an effect on TS- mutant FM3A cells which was almost as lethal as the effect on wild-type FM3A cells in the presence of thymidine. Therefore, this lethal effect could be attributable to the inhibition of RNA metabolism, rather than DNA metabolism. The effects of 5-FU on RNA metabolism in L1210 cells are as follows: (1) inhibition of the processing of preribosomal RNA to ribosomal RNA (2) inhibition of the synthesis of poly(A) RNA of mRNA (3) inhibition of tRNA methylation (4) impaired synthesis of snRNA, U4, U6. (5) inhibition of pre-rRNA methylation (6) enhancement of poly(A) RNA translation. With reference to the items listed above, a discussion was made on the basis of our experimental results.
Kanamaru
R
R
Dept. of Clinical Cancer Chemotherapy, Research Institute for Tuberculosis and Cancer, Tohoku University.
Wakui
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology; D007939:Leukemia L1210 / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism*
D000970:Antineoplastic Agents; D012334:RNA, Neoplasm; D005472:Fluorouracil