Formate overflow coupled to mitochondrial oxidative metabolism\ has been observed in cancer cell lines, but whether that takes place in the tumor microenvironment is not known. Here we report the observation of serine catabolism to formate in normal murine tissues, with a relative rate correlating with serine levels and the tissue oxidative state. Yet, serine catabolism to formate is increased in the transformed tissue of in vivo models of intestinal adenomas and mammary carcinomas. The increased serine catabolism to formate is associated with increased serum formate levels. Finally, we show that inhibition of formate production by genetic interference reduces cancer cell invasion and this phenotype can be rescued by exogenous formate. We conclude that increased formate overflow is a hallmark of oxidative cancers and that high formate levels promote invasion via a yet unknown mechanism.

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Aged pea Pisum sativum L. var Alaska epicotyl tissue was wounded by excising the apical 10 or 20 millimeters and incubating the excised segments upright in buffer. Wounding induced a very rapid formation of polysomes which was accompanied by minor increases in ribosomes, mRNA, and poly(A) and by a doubling of the in vivo protein synthesizing capacity. This increase in protein synthesis in vivo was matched by a similar increase in polypeptide synthesis in vitro in wheat germ reactions primed by polysomes. However, in vitro reactions primed by total and polysomal RNA from wounded tissue were affected much less.Two-dimensional gel patterns of silver-stained proteins accumulated in vivo were almost unchanged, even after 6 hours of wounding, since only two spots decreased in intensity and none increased. In contrast, two-dimensional gel fluorographs of polypeptides generated in vitro by both total RNA and polysomal RNA showed numerous changes within 3 hours of wounding. Of the more than 200 spots visualized by fluorography, 17 decreased and 26 increased when total RNA from wounded tissue was used; 15 decreased and 10 increased when polysomal RNA was used. Those polypeptides that decreased after wounding were generally of lower molecular weight; those which increased were of higher molecular weight.Although wounding must be affecting transcription insofar as different mRNAs must be present to encode different polypeptides, its major effect appears to be on translation, presumably through formation of ribosomes with greater translational efficiency.

The genomic DNAs of the eukaryotic Chlorella-like green alga, strain NC64A, and eleven of its viruses all contain significant levels of 5-methyldeoxycytidine. In addition, the host DNA as well as six of the viral DNAs also contain N6-methyldeoxyadenosine. At least some of the methylated bases in the host reside in different base sequences than the methylated bases in the viruses as shown by differential susceptibility to restriction endonuclease enzymes. This suggests that the viruses encode for DNA methyltransferases with sequence specificities different from that of the host enzyme.

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