PMID: 9539775May 16, 1998Paper

Selective killing of preneoplastic and neoplastic cells by methotrexate with leucovorin

Proceedings of the National Academy of Sciences of the United States of America
M Chow, H Rubin

Abstract

Three sublines of NIH 3T3 cells had the properties of non-neoplastic, preneoplastic, and neoplastic cells, respectively. The closer the cells were to neoplastic behavior, characterized by continuing growth at high density, the slower they multiplied at lower density. Under the conditions of high population density and low calf serum concentration used in the assay for transformed focus formation, the transformed or neoplastic cells were much more sensitive to killing by methotrexate (MTX) than were non-neoplastic cells in the same culture. This differential sensitivity of neoplastic cells was far more pronounced in molecular, cellular, and developmental biology medium 402 (MCDB 402) than in DMEM. It is associated with the presence in MCDB 402 of folinic acid, known clinically as leucovorin, which is a reduced form of the folic acid present in DMEM. Although leucovorin had been shown to selectively spare normal bone marrow and intestine in animals from the killing effect of MTX on tumor cells, we demonstrate the preferential killing of neoplastic over non-neoplastic cells of the same derivation. Neither neoplastic nor non-neoplastic cells were killed once they had stopped multiplying at their respective saturation densities. The...Continue Reading

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Citations

Aug 26, 1999·In Vitro Cellular & Developmental Biology. Animal·M Chow, H Rubin
Jan 12, 2000·Journal of Chromatography. B, Biomedical Sciences and Applications·A SparreboomJ Verweij
Aug 5, 2000·Environmental Toxicology and Pharmacology·R C ChoudhuryA K Palo
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·M Chow, H Rubin
Nov 7, 2021·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Nikki de RouwRob Ter Heine

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