Folic acid analogs and the growth of embryo and tumor tissue.

Analogs of pteroylglutamic acid (folie acid) have been extensively investigated from both the standpoint of their preparation and their biological effects. Numerous compounds of this type have been synthesized and their effects tested with re spect to the growth of various animals and tissues. The present status of this field of research has been summarized in some of the contributions to the recent series of papers on anti-metabolites given under the auspices of the New York Acad emy of Sciences (2-6, 9). It is generally considered that these compounds, when introduced into an animal, serve as an tagonists of folie acid and especially affect those tissues which are sensitive to an insufficiency of this vitamin. It has also been demonstrated that there is a wide variation in the dosage of the avail able analogs required to block out folie acid from the cells (4, 5, 7). A number of folie acid analogs have been tested on malignant neoplasms (9, 10). It has been found that growth inhibition may result from the ap plication of these compounds. 4-Aminopteroylglutamic acid (aminopterin) has proved especially effective in this regard. However, non tumor tissue is also adversely affected. Other less toxic folie acid analogs such as pteroyltriglutamic acid (teropterin) and pteroylaspartic acid (An-Fol-A) have been found to be less effective, even at com paratively large dosages. Stock (9) and associates found that teropterin was ineffective on eggcultivated tumors when dosages as high as 20 mg. per injection were used. Such data as are available indicate that different types of tumors do not re act similarly to such compounds. Sugiura (10) and co-workers have reported that aminopterin had an inhibitory effect at toxic levels on transplants of a sarcoma in rats and on a sarcoma, mammary carcinoma, and melanoma in mice. Spontaneous breast tumors in mice were not affected. The present investigation was undertaken to test representatives of folie acid analogs on the growth of embryo and yolk sac tumors of tumor-