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Effect of methotrexate on cell proliferation in developing hamster molar tooth germs in vitro
Author(s) -
Wöltgens Joseph H. M.,
Lyaruu Donacian M.,
Bronckers Antonius L. J. J.,
Duin Marion A.,
Bervoets Theodor J. M.
Publication year - 1998
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/j.1600-0722.1998.tb02169.x
Subject(s) - thymidine , cell growth , methotrexate , hamster , in vitro , dna synthesis , cell , molar , chemistry , cell culture , microbiology and biotechnology , biochemistry , biology , endocrinology , immunology , paleontology , genetics
Amongst the most frequently used drugs for the treatment of acute lymphoblastic leukaemia (ALL) belongs methotrexate (MTX), an inhibitor of pyrimidine (thymidine) synthesis. We examined effects of MTX on cell proliferation during tooth morphogenesis in organ culture by exposing hamster molar tooth germs to 10 −7 to 10 −3 M MTX for 24 h. In the presence of serum, only the highest concentration of MTX (10 −3 M) induced a small, non‐significant decrease in cell mass without histological changes but, unexpectedly, increased uptake of [ 3 H]thymidine. In serumless conditions increase in cell mass (dry weight) and incorporation of [ 3 H]thymidine was lower than in serum‐supplemented conditions. Exposure to MTX in serumless conditions reduced the increase in cell mass even further without histological changes and, again, strongly enhanced incorporation of [ 3 H]thymidine to the same proportion as measured in the serum‐supplemented cultures exposed to MTX. The data suggest that only exposure to high levels of MTX reduces proliferation activity, shown by reduction in cell mass. The enhanced [ 3 H]thymidine uptake under MTX exposure was explained by blockage of the internal biosynthesis of thymidine, by which action more radiolabel was taken up from the medium. The data also suggest that serum contains (growth) factors that stimulate cell proliferation, thereby increasing cell mass and [ 3 H]thymidine incorporation.