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Ribonuclease Activity and Cancer: A Review^*

Jay S. Roth

( Institute of Cellular Biology, University of Connecticut, Storrs, Connecticut)

In reviewing the work reported herein under the various major sections, one can gain only some general impressions:

1. Ribonuclease activity in tumors.—There appears to be a tendency for RNase activity in a number of rapidly growing tumors to be lower than in the normal tissue of origin. In the transplantable hepatoma this appears to be particularly true of RNase activity associated with the mitochondrial fraction. There are many exceptions to these observations, however, in which normal or higher than normal activity has been found, so that at the present time, no general conclusions can be drawn.

2. Ribonuclease activity during carcinogenesis and in primary tumors resulting from drug feeding.—Most observations have been made on liver; determinations have been made with such a variety of experimental conditions that it is difficult to find a consistent pattern. Nevertheless, there appears to be fairly general agreement that there is a rise in specific activity of acid RNase, generally in the supernatant fraction. Changes in alkaline RNase are variable, depending on conditions.

3. Ribonuclease in sera of tumor-bearing animals.—In a limited number of observations, mostly on humans, there appears to be general agreement that RNase activity is increased in the serum of the tumor-bearing animal.

4. The effect of injection of crystalline pancreatic ribonuclease on tumor growth.—In a moderately large sampling of observations with different tumors, relatively large amounts of crystalline RNase did have a rather specific tumor-retarding action. Only a few exceptions were noted, which, in view of the differences in conditions, is not surprising. These results suggest possible usefulness of this enzyme in clinical cases, and clinical trial is presumably under way.

5. The relation of ribonuclease activity to growth.—In bacteria, plants, and some mammalian tissues, increased growth was associated with increased RNase activity. In one exception, it appeared that lowered RNase activity favored tumor growth (2, 76).

In spite of a report to the contrary, there appears to be little question that tumor cells do contain RNase. It is doubtful whether the relationships between RNases and RNase inhibitor and cancer can be delineated without further understanding of the properties and functions of these substances in normal cells. Studies of the relationships among growth, RNA metabolism, and RNase activity in normal plant, bacterial, and animal cells are proving helpful and should be continued.

The finding of considerably increased RNase inhibitor activity in Dunning hepatoma may provide an experimental approach to the discovery of the function of this interesting material, and it has been suggested that it may be related to turnover of RNA (68).

The well known association of RNase with ribosomes of both E. coli and rat liver also provides a possible approach to determining a relationship between RNase and protein synthesis, and there have been many publications in this area in the past few years which, however, have not yet clearly indicated a relationship.

The availability of many transplantable rat hepatomas with greatly varying biochemical and cytological properties should prove helpful, and it is expected that additional studies on the RNase activities of such tumors will be carried out. As yet, there are relatively few observations on primary tumors or, particularly, "spontaneous" tumors in animal and man, and investigations with these should be extended. Further studies on RNase activity in the sera of tumor-bearing animals and humans appear to be warranted. RNase activities in leukemic cells have also received little attention.

Increased development and refinement of histochemical technics at the microscopic and electron microscopic level are much to be desired, and it is probable that this will occur in the near future and help to determine the specific location of the enzymes in cells.

For those working in the field, it is somewhat reassuring to know that scarcely a beginning has been made in our understanding of the relationship of RNase activity to cancer or even to RNA metabolism in the normal cell.

^* Research of the author described herein was supported by grants from the American Cancer Society and the National Cancer Institute, National Institutes of Health.

Senior Career Investigator, National Cancer Institute, National Institutes of Health.

Received 11/ 5/62.