Cellular xanthine oxidase and uricase levels in leukemic and normal mouse leukocytes.

Quantitative alterations in the purine catabolic enzyme, xanthine oxidase, have been observed in neoplasia and nonmalignant hyperplasia. A decrease in the xanthine oxidase level per cell during carcinogenesis in both liver and breast tumors has been reported (1, 8). Likewise, Bennett and associates ~ have shown that several experimental tumors are low in xanthine oxidase activity. In contrast, the rapid cellular proliferation during liver regeneration is associated with a doubling of the cellular xanthine oxidase levels (4). An elevated xanthine oxidase level is therefore characteristic of normal hyperplastic liver, whereas diminished xanthine oxidase levels seem to be characteristic of rapidly growing hepatoma and of other neoplasms. To determine whether the decrease in purine catabolic enzymes accompanying neoplasia is a general phenomenon, it is important to compare other rapidly growing normal tissues with their malignant counterparts. The experimental mouse ascitic leukemia LI~10 provides just such an experimental opportunity. The xanthine oxidase and uricase activities of these leukemic cells were therefore compared with those of rapidly developing lymphocytes derived from normal mouse spleen and with normal polymorphonuclear leukocytes. Since previous studies have demonstrated inhibition of xanthine oxidase by pharmacological levels of 8-azaguanine in vitro and in vivo (5, 9), the enzymatic basis underlying 8-azaguanine sensitivity and dependence of sublines of LI~10 cells was also investigated. The hypothesis that differential 8-azaguanine sensitivity in the sensitive and dependent sublines is due to variations in the cellular levels of xanthine oxidase was tested.