Open AccessTHE EFFECT OF VINCRISTINE ON MOUSE JEJUNAL CRYPT CELLS OF DIFFERING CELL AGE: DOUBLE LABELLING AUTORADIOGRAPHIC STUDIES USING 3 H‐ AND 14 C‐TdR
Author(s) -
Jellinghaus W.,
Schultze B.,
Maurer W.
Publication year - 1977
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.1365-2184.1977.tb00140.x
Subject(s) - crypt , in vivo , hela , mitosis , cell cycle , metaphase , biology , in vitro , cell synchronization , mitotic index , interphase , cell division , cell , microbiology and biotechnology , thymidine , biochemistry , genetics , chromosome , endocrinology , gene
The mechanism of action of the alkaloid vincristine (VCR) has been investigated in vitro on HeLa cells in culture and in vivo on jejunal crypt cells of the mouse. The in vitro experiments with HeLa cells show that VCR affects not only mitotic but also interphase cells. The VCR‐affected cells first continue their passage through the cell cycle undisturbed but after reaching mitosis they are arrested in metaphase. This agrees well with the results obtained by Madoc‐Jones & Mauro (1968) and Madoc‐Jones (1973) on synchronized cell cultures. Until now there has been no investigation of the mechanism of action of VCR in vivo . This is due to the absence of a suitable technique for synchronization in vivo . The present study is based on a method which permits the assessment of the VCR sensitivity as a function of the cell age without synchronization in the usual sense. The jejunal crypt epithelium of the normal mouse was double labelled with 3 H‐ and 14 C‐thymidine (TdR) in such a way as to produce a narrow subpopulation of crypt cells with a maximum age difference of 1 hr. On autoradiographs these cells can be distinguished by their characteristic labelling from other cells. As this ‘pseudo’‐synchronized subpopulation passes through the cycle the effect of VCR can be studied, i.e. one can analyse the effect in well‐defined time intervals of the cycle. The results show that the effect of VCR is the same in vivo as in vitro . The crypt cells which are affected by VCR in interphase continue their passage through the cycle, but upon entering mitosis they are arrested in metaphase. VCR has, at the concentration used in the present study, no effect on the duration of the S and G 2 phases. The necrotic cells seen after VCR application are formed from arrested metaphases.