The requirements for amino acids, vitamins, pyrimidines, purines, and glucose of the sensitive Streptococcus faecalis (ATCC 8043) were compared with those of four mutants selected for their resistance to 5-fluorouracil, 5-fluorouridine, 5-fluoro-2′-deoxyuridine, and 5-fluoro-2′-deoxycytidine. The observed differences could be correlated with a shift toward the increased biosynthesis of metabolites which can reverse the growth inhibition caused by the active intermediate, 5-fluoro-2′-deoxyuridylic acid. The increase in the metabolic activity of a mutant is a reflection of the extent to which the corresponding analog is converted to the active intermediate. No differences in the rate of uptake of 5-fluorouracil were observed between the sensitive or resistant strains. Resistance to a fluoropyrimidine is accompanied by complete cross-resistance to the less potent fluoropyrimidines and by partial resistance toward the more potent fluoro-derivatives.
These studies were supported in part by Contract No. SA-43-ph-2445 from the Cancer Chemotherapy National Service Center, National Cancer Institute, National Institutes of Health; and by Grant T-107 from the American Cancer Society. The senior author was a Predoctoral Fellow supported by training grant CRTY-5015 from the National Cancer Institute.