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Biochemical Alterations during Unperturbed Suspension Growth of L1210 Cells¹

Departments of Medicine and Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510

The following parameters were evaluated at several points throughout unperturbed suspension culture growth of L1210 cells: cell volume; DNA histograms; the mean content of cellular DNA, RNA, and protein; ribonucleoside and deoxyribonucleoside triphosphate pools; phosphoribosyl pyrophosphate; and the incorporation of glycine into purine bases. The cell volume, the incorporation of glycine into purine bases, and the intracellular pools of phosphoribosyl pyrophosphate and deoxyribonucleotides began to decrease significantly during the midportion of logarithmic cell growth. However, there was no significant change in the DNA content per cell during culture growth. The RNA, protein content, and ribonucleotides all demonstrated a biphasic pattern with the highest values obtained during the midportion of logarithmic growth followed by a rapid decline as the culture approached plateau growth. These intracellular fluctuations in de novo synthesis and precursor pools were correlated with the variable intracellular accumulation of three fluoropyrimidines (5-fluorouracil, 5-fluorouridine, and 5-fluorodeoxyuridine) and their active metabolites (5-fluorouridine triphosphate and 5-fluorodeoxyuridylate). These studies were performed to demonstrate that multiple biochemical alterations occur during logarithmically growing suspension cell cultures and could result in misleading conclusions of experiments with antimetabolites unless these factors are considered in the context of the performed studies.

¹ Supported by Grant CH-145 from the American Cancer Society, a Swebilius Cancer Award from the Yale Comprehensive Cancer Center, and National Cancer Institute Grants CA-27130 and CA-08341.

² Recipient of Young Investigator Award CA-24187 from the National Cancer Institute.

³ To whom requests for reprints should be addressed.

Received 5/ 5/80. Accepted 10/ 9/80.