Open AccessCell Position Dependence of Labelling Thymidine Nucleotides Using the De Novo and Salvage Pathways In the Crypt of Small Intestine
Author(s) -
Chwalinski S.,
Potten C. S.
Publication year - 1986
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.1986.tb00764.x
Subject(s) - crypt , thymidine , nucleotide salvage , dna synthesis , thymidine kinase , biology , biochemistry , de novo synthesis , deoxyuridine , dna , microbiology and biotechnology , nucleotide , chemistry , enzyme , immunology , endocrinology , gene , virus , herpes simplex virus
. About twice as much tritiated thymidine ([ 3 H]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 ([ 3 H]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 [ 3 H]UdR, but has no effect on [ 3 H]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 [ 3 H]TdR into DNA. the increased efficiency of thymidine utilization by crypt base cells is not attributable to (i) differences in accessibility of thymidine; (ii) differences in the rate of DNA synthesis or (iii) the size of the nuclei.