当前位置： SCI文献检索 > CANCER RESEARCH期刊下所有文献 > Antitumor activity of cytidine dialdehyde and its effects on nucleotide and nucleic acid synthesis.

Antitumor activity of cytidine dialdehyde and its effects on nucleotide and nucleic acid synthesis.

Abstract：

:Cytidine dialdehyde inhibited the growth of leukemia L1210 cells in culture at a 50% inhibitory concentration of 3.5 X 10(-5) M and, when administered i.p. at 200 mg/kg daily for 5 days, increased the mean survival of L1210 tumor-bearing mice by up to 171%. Given by the s.c. or i.v. routes, the compound was ineffective. The ethanol adduct of cytidine dialdehyde, although inactive in cell culture, increased the mean survival of L1210 tumor-bearing mice by up to 225% when administered i.p. but was inactive upon s.c. administration. Exposure of L1210 cells in culture for 25 hr to cytidine dialdehyde at the 50% inhibitory concentration increased the ribonucleoside di- and triphosphate pools, slightly increased deoxyadenosine triphosphate, deoxythymidine triphosphate, and deoxyguanosine triphosphate pools, and caused a pronounced increase in the deoxycytidine triphosphate pool. As determined by the rate of pyrimidine precursor incorporation into nucleic acids, this concentration of drug showed no effect on RNA synthesis but caused a reduction in DNA synthesis to 53% of control. Exposure of L1210 cells for 3 to 6 hr to 10(-4) M cytidine dialdehyde, a concentration which inhibits growth completely, effected an increase in the ribonucleoside di- and triphosphate pools and a rapid decrease of the deoxythymidine triphosphate pool. The deoxycytidine triphosphate and deoxyguanosine triphosphate pools decreased more slowly, and the deoxyadenosine triphosphate pool remained slightly elevated. Analysis of the rate of substrate incorporation into nucleic acids showed that this concentration of drug produced an 80% decrease in RNA synthesis and a 75% decrease in DNA synthesis 3 hr after drug exposure. These results suggest that the mechanism of action of cytidine dialdehyde may be due to its initial interference with DNA synthesis followed by a generalized inhibition of DNA, RNA, and protein synthesis at cytotoxic concentrations.

journal_name

Cancer Res

journal_title

Cancer research

authors

Kinahan JJ,Pavelic ZP,Leonard RJ,Bloch A,Grindey GB

subject

Has Abstract

pub_date

1980-03-01 00:00:00

pages

598-603

issue

eissn

0008-5472

issn

1538-7445

journal_volume

pub_type

杂志文章

在线工具

Antitumor activity of cytidine dialdehyde and its effects on nucleotide and nucleic acid synthesis.