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In the present study, the expressions of p53 and N-myc gene were analyzed immunohistochemically in rat ovarian tumors induced by 7,12 dimethylbenz (a) anthracene (DMBA). 1) p53 could be seen in the nucleolei of tumor cells. The positive rates were: adenomas 17%, adenocarcinomas 37%, sarcomas 0%, mixed müllerian tumor 0% and epidermal cysts 100%. Neither the serial-allografted tumor nor DMBA-OC-1 was positive. 2) N-myc could be seen in the cytoplasm and perinuclear cytoplasm of tumor cells. The positive rates were: adenomas 33%, adenocarcinomas 77%, sarcomas 100%, mixed müllerian tumors 100% and epidermal cysts 100%. Both the serial-allografted tumor and DMBA-OC-1 were positive. 3) The positive rates in both p53 and p21 were: adenocarcinoma 20% and epidermal cysts 100%. The positive rates in both N-myc and p21 at the were: adenoma 17%, adenocarcinoma 50%, sarcoma 33%. Both the serial-allografted tumor and DMBA-OC-1 were positive. Only two cases were positive for p53, N-myc and p21. p53 was detected in most of the adenomas. 4) The positive rate for both N-myc and p21 was higher than that for both p53 and p21. This was similar to other reports. The results suggested that p53 plays a role in precancerous tumor as a recessive oncogene. It was supposed that tumors with N-myc gene expression were had malignant growth characteristics.

Clonal evolution which characterizes malignant tumors is the consequence of two antagonizing forces acting on the tumor cell population, namely, forces of diversion and conversion. The former makes cells to diverge through genetic and epigenetic instabilities which are the built-in characteristics of malignant cells. Possible causes of genetic instability are discussed. These include mistakes in DNA synthesis by an error-prone DNA polymerase, the nucleotide pool distartion and the overreplication of replication origins, abnormal DNA repair, high rate recombination, by expression of fragile sites and possibly by expression of retrotransposons, frequent nondisjunction of chromosomes as a consequence of gene dosage inbalance, and abnormal DNA methylation. The second force makes the resulting tumor cell population with heterogenous phenotypes to converge through selection by host defence mechanisms, competition for nutrients and oxygen among tumor cells, to cell interactions within tumor and between surrounding normal tissues. Genetic tagging of tumor cells with pSV 2neo facilitates the analysis of clonal evolution which results from diversion and conversion of tumor cells. Selective growth and metastasis of a clone in a mouse sarcoma population was demonstrated. Generation of dominant clones as well as drug resistant clones in tumor can be studied with this method.