The lactate dehydrogenase ( L D H ) isornzyme pattern of the turnour-bearing colon has been studied in homogenates by disc-electrophoretic separation. The preponderance of M-L D H in malignant tissue has been confirmed.It has been shown that the isoenzyme pattern may be altered in the absence of morphological changes. Thus, the metabolic change is not specifically dependent on the existence of tumorous parenchymatous changes as currently recognized by light microscopy.It is suggested that the tumour develops within a tissue where metabolic modifrcations may precede the stage of morphological malignancy.It appears, therefore, that the alteration of the enzyme pattern might be symptomatic of an established, but very early, neoplastic cona'ition, the microscopic recognition malignancy being a later development.
The incorporation of 2-[35S]thiouracil and two of its derivatives into murine melanomas, in vivo, was studied. It was confirmed [J. R. Whittaker, J. Biol. Chem., 246, 6217--6226 (1971)] that 2-thiouracil has a marked affinity for melanin-producing tissue and that an affinity for such tissue could be sustained by 5-substituted 2-thiouracils. A series of derivatives of arotinoids and retinoids, with or without a 2-thiouracil group as a potential carrier to obtain affinity for melanomas, was examined for cytostatic activity, in vitro. None of these showed significant activity against murine melanomas.
The lactate dehydrogenase isoenzyme pattern of biopsies from Indian oral leukoplakia, submucous fibrosis and carcinoma of the oral mucosa as well as that of oral mucous membrane biopsies from clinically normal Indian persons has been studied. The LDHIV/LDHII isoenzyme ratios found for leukoplakias, carcinomas and control biopsies did not differ significantly. The mean isoenzyme ratio of Indian control biopsies was significantly above that reported for Danish control biopsies. Submucous fibrosis was accompanied by a significant depression of the isoenzyme ratio. No clear correlation between LDH isoenzyme pattern and epithelial thickness was found. Smoking and chewing habits, which may be correlated with prevalence and localization of oral leukoplakias and carcinomas, did not significantly influence the isoenzymatic structure. Although final conclusions cannot be drawn, the high isoenzyme ratio of the Indian control material may represent an early precancerous condition, unrelated to smoking and chewing, preceding the histopathological manifestations of precancerous lesions.
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