INTERACTION BETWEEN 3 SUBPOPULATIONS OF EHRLICH CARCINOMA IN MIXED SOLID TUMORS IN NUDE-MICE - EVIDENCE OF CONTACT DOMINATION

Clonal interaction between three subpopulations of Ehrlich carcinoma w ere studied during growth as mixed solid tumours and as ascites tumour s in immune-incompetent nude NMRI mice. The tumour cell lines differed in DNA content as determined by DNA flow cytometry (FCM). Tumour grow th was evaluated by tumour growth curves including calculation of tumo ur volume doubling times, tumour weight on day 14, cell cycle times (p er cent labelled mitoses) and cell cycle distributions (FCM). Two subp opulations (E1.15 and E1.95) showed nearly identical growth characteri stics during both solid and ascites tumour growth. The third subpopula tion (E1.80) grew more slowly. FCM on fine-needle tumour aspirates was used to determine the relative proportions of the cell populations in mixed solid tumours in which E1.95 showed a growth-dominating effect on E1.15. No such effect was demonstrated during single-cell tumour gr owth in ascitic fluid in which the cells had no intimate contact. Asci tic fluid from E1.95-bearing animals or radiation-killed E1.95 cells h ad no effect on the growth of E1.15, and no remote effect was seen whe n the two cell lines were growing in opposite flanks. This indicates t hat only viable E1.95 cells in close in vivo contact were able to indu ce growth inhibition of the E1.15 subpopulation. Both the E1.95 and th e E1.15 cells dominated the E1.80 cells, but in these cases cell kinet ic differences may have played a role as the E1.95 and the E1.15 lines grew faster than the E1.80. The E1.80 cell line had no dominating eff ect on the E1.15 or E1.95. It is concluded that non-immunologically me diated cellular dominance in heterogeneous tumours may contribute to t he evolution of these tumours and may be involved in fundamental tumou r biological phenomena.