Comparison of pyrimidine nucleotide synthetic enzymes involved in 5-fluorouracil metabolism between human adenocarcinomas and squamous cell carcinomas
✍ Scribed by Yoshihiko Maehara; Sunao Moriguchi; Yasunori Emi; Akihiro Watanabe; Shunji Kohnoe; Shunichi Tsujitani; Keizo Sugimachi
- Publisher
- John Wiley and Sons
- Year
- 1990
- Tongue
- English
- Weight
- 612 KB
- Volume
- 66
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
The activities of orotate phosphoribosyltransferase (OPRT), cytidine triphosphate (CTP) synthetase, deoxycytidine monophosphate (dCMP) deaminase, thymidine monophosphate (dTMP) kinase, uridine (Urd) kinase, thymidine (dThd) kinase, Urd and dThd phosphorylases, and DNA polymerase were examined in the eight human lung squamous cell carcinomas and five lung adenocarcinomas, and five tumoradjacent normal lung tissues. All of these enzymes are involved in pyrimidine nucleotide synthesis. The metabolism of 5-fluorouracil(5-FU) was determined. The levels of these enzymes, except for OPRT, were high in tumor tissues and almost the same between lung squamous cell carcinomas and adenocarcinomas, with no statistical difference. The activities for phosphorylation and degradation of 5-FU were similar in each tissue type of tumor. As 5-FU is incorporated into tumor cells and is metabolized actively to 5-FU nucleotides in squamous cell carcinoma tissues, at almost the same level seen in adenocarcinoma tissues, this drug should have a wide clinical application. Cancer 66:156-161,1990. HE DRUG, 5-FLUOROURACIL (5-FU), is phosphory-T lated to 5-FU nucleotides,'" via three enzymatic pathways involved in pyrimidine n ucleotide synthesis. 3*4 Thymidine monophosphate (dTMP) synthase (EC 2.1.1.45), DNA synthesis,5 and RNA synthesis6 are inhibited and cell death follows. The sensitivity of human tumor tissues to 5-FU differs with the tissue7,' and depends on the enzyme activities involved in the pyrimidine nucleotide synthe~is.~ 5-Fluorouracil and its analogues are prescribed to treat adenocarcinoma, i. e., gastrointestinal" and breast cancers." Also, 5-FU is used for squamous cell carcinomas in combination with other antitumor drugs. '*-I4 Lung squamous cell carcinomas appear to be chemotherapy-resistant tumors.'5'16