The function of the Leuconostoc citrovorum factor in cell division and the inactivation of aminopterin

Abstract

As previously recorded (Jacobson, 1954), folic acid antagonists such as aminopterin and A-methopterin arrest mitosis in metaphase; it was also found that certain types of cells are able to overcome this inhibition on more prolonged exposure to the agents. The present study was undertaken with two main objects, (a) to find whether the inhibition of mitosis by the folic acid antagonists is of an unspecific nature or whether it is due to interference with the normal function of a particular substance within the cell; and (b) to discover why certain tissues gradually become 'resistant' to the antagonists.The results showed that the agents probably interfere with the intracellular activity, not of folic acid itself, but of one of its derivatives, viz. the Leuconostoc citrovorum factor (LCF) a 5-formyl, 5: 6: 7: 8-tetrahydro derivative of folic acid. That some tissues gradually become resistant to folic acid antagonists might have been due to either of two alternatives: (1) the cells might use another metabolic pathway, by-passing the block caused by the antagonist and rendering the action of LCF no longer essential for cell division; or (2) the cells might inactivate the inhibitor. As described below, the latter alternative was found to be correct. Structural formulae of the pteridine compounds used in this work are shown in Fig.

Effect of Folic Acid Analogues on Growth and Cell Division of Nonexacting Microorganisms

“…In addition to the many dependent metabolic processes, folic acid, or the coenzyme form of folic acid, appears essential for mitosis in avian and mammalian cells. Recent work by Jacobson (1954aJacobson ( , 1954b has shown that the addition of aminopterin to osteoblasts or fibroblasts in tissue culture causes a specific arrest of mitosis at metaphase. This inhibition can be counteracted by the citrovorum factor (leucovorin) but not by folic acid.…”

Drug Resistance in Protozoa

“…Moreover, it has been shown that compounds whose inhibitory action is directed against p-AB-folk acid metabolism affect nuclear division. folinic acid) but not by folic acid (Jacobson, 19543). I n cultures of embryonic chick fibroblasts and osteoblasts it has been observed to prevent the completion of mitosis by arresting this process at the metaphase (Jacobson, 1954a), and this action could be overcome by Leuconostoc citrovorum factor (i.e.…”

“…I n cultures of embryonic chick fibroblasts and osteoblasts it has been observed to prevent the completion of mitosis by arresting this process at the metaphase (Jacobson, 1954a), and this action could be overcome by Leuconostoc citrovorum factor (i.e. folinic acid) but not by folic acid (Jacobson, 19543).…”