Cell position dependence of labelling thymidine nucleotides using the de novo and salvage pathways in the crypt of small intestine.
dc.contributor.author | Chwalinski, S | |
dc.contributor.author | Potten, Christopher S | |
dc.date.accessioned | 2010-11-30T18:16:40Z | |
dc.date.available | 2010-11-30T18:16:40Z | |
dc.date.issued | 1986-11 | |
dc.identifier.citation | Cell position dependence of labelling thymidine nucleotides using the de novo and salvage pathways in the crypt of small intestine. 1986, 19 (6):647-59 Cell Tissue Kinet | en |
dc.identifier.issn | 0008-8730 | |
dc.identifier.pmid | 3802186 | |
dc.identifier.uri | http://hdl.handle.net/10541/116790 | |
dc.description.abstract | About twice as much tritiated thymidine ([3H]TdR) is taken up by cells at the bottom of the crypt of the small intestine as by the rapidly cycling mid-crypt cells. However, the uptake of tritiated deoxyuridine ([3H]UdR) is even throughout the crypt. Exogenous thymidine is incorporated about four times and eight times more efficiently than deoxyuridine by the cells in the mid-crypt and cells at the bottom of the crypt, respectively. However all S phase cells in the crypt appear to be capable of using either precursors, i.e. either the de novo or salvage pathway. Since methotrexate (1 or 5 mg/kg) inhibits (at 5 mg/kg completely) the uptake of [3H]UdR, but has no effect on [3H]TdR uptake, the de novo and salvage pathways appear to be independent. Within the precision of the methods used in the experiments the 3 hr inhibition of the de novo pathway of deoxythymidylic acid (dTMP) synthesis by methotrexate does not produce any increase in utilization of the salvage pathway measured by incorporation of [3H]TdR into DNA. The increased efficiency of thymidine utilization by crypt base cells is not attributable to differences in accessibility of thymidine; differences in the rate of DNA synthesis or the size of the nuclei. It appears that crypt base cells (which include the putative stem cells) are efficient scavengers of [3H]TdR, and this might be related to the level of thymidine kinase activity within the cells, and/or to changes in the availability of endogenous thymidine (break-down products) which compete with exogenous [3H]TdR.(ABSTRACT TRUNCATED AT 250 WORDS) | |
dc.language.iso | en | en |
dc.subject.mesh | Animals | |
dc.subject.mesh | Deoxyuracil Nucleotides | |
dc.subject.mesh | Intestinal Mucosa | |
dc.subject.mesh | Intestine, Small | |
dc.subject.mesh | Male | |
dc.subject.mesh | Methotrexate | |
dc.subject.mesh | Mice | |
dc.subject.mesh | Thymidine | |
dc.subject.mesh | Thymidine Kinase | |
dc.subject.mesh | Thymidine Phosphorylase | |
dc.title | Cell position dependence of labelling thymidine nucleotides using the de novo and salvage pathways in the crypt of small intestine. | en |
dc.type | Article | en |
dc.contributor.department | Paterson Institute Laboratories, Manchester, M20 9BX. UK. | en |
dc.identifier.journal | Cell and Tissue Kinetics | en |
html.description.abstract | About twice as much tritiated thymidine ([3H]TdR) is taken up by cells at the bottom of the crypt of the small intestine as by the rapidly cycling mid-crypt cells. However, the uptake of tritiated deoxyuridine ([3H]UdR) is even throughout the crypt. Exogenous thymidine is incorporated about four times and eight times more efficiently than deoxyuridine by the cells in the mid-crypt and cells at the bottom of the crypt, respectively. However all S phase cells in the crypt appear to be capable of using either precursors, i.e. either the de novo or salvage pathway. Since methotrexate (1 or 5 mg/kg) inhibits (at 5 mg/kg completely) the uptake of [3H]UdR, but has no effect on [3H]TdR uptake, the de novo and salvage pathways appear to be independent. Within the precision of the methods used in the experiments the 3 hr inhibition of the de novo pathway of deoxythymidylic acid (dTMP) synthesis by methotrexate does not produce any increase in utilization of the salvage pathway measured by incorporation of [3H]TdR into DNA. The increased efficiency of thymidine utilization by crypt base cells is not attributable to differences in accessibility of thymidine; differences in the rate of DNA synthesis or the size of the nuclei. It appears that crypt base cells (which include the putative stem cells) are efficient scavengers of [3H]TdR, and this might be related to the level of thymidine kinase activity within the cells, and/or to changes in the availability of endogenous thymidine (break-down products) which compete with exogenous [3H]TdR.(ABSTRACT TRUNCATED AT 250 WORDS) |