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Correlation of in Vivo Cancer, Net Outer Charge, in Vitro Migration, Interferon Activity, in Vitro Growth Rates, and Chalone-like Activity to Transformation-Reversion in Cloned Moloney and Kirsten Sarcoma Virus-transformed Mouse 3T3 Cells¹

Institute of Medical Microbiology, University of Copenhagen [P. E., L. O., O. R., G. K.], and Institute of Medical Microbiology, University of Arhus [S. H.], Denmark

The effect of malignant transformation and reversion on various cell characteristics was studied in cloned Moloney and Kirsten sarcoma virus-infected, non-virus-producing mouse 3T3 cells. Transplantation of down to one morphologically transformed cell showed in vivo cancer, whereas this was undetectable with 10⁷ revertant or normal cells. Both transformed and one revertant NIH cell lines showed slower in vitro growth than did uninfected cells, whereas growth rates of the BALB 3T3 cells were unaffected by transformation-reversion. Transformation resulted in a less negative net outer charge. Upon reversion of transformed NIH 3T3 cells, the charge normalized, whereas it remained altered in revertant BALB 3T3 cells. In vitro migration for 24 hr in medium with or without fetal calf serum appeared to be unrelated to transformation. The production of virus-inhibitory activity (interferon) after challenge with West Nile virus or Newcastle disease virus was enhanced in transformed and some revertant cells. Chalone-like DNA synthesis-inhibitory extracts (M.W., 20,000 to 50,000) were prepared from cells and medium of all cultures, and each extract was tested on its cell of origin. No effect was found with cell extracts harvested from confluent cultures, whereas cell extracts from subconfluent cultures had a DNA synthesis-inhibitory effect on all cell types, except Kirsten sarcoma virus-transformed BALB cells, in which no response was obtained. In contrast to the cells, medium fraction exhibited more DNA-inhibiting activity when harvested from confluent, rather than from subconfluent, cultures.

¹ This investigation was supported by Dr. R. Rask-Nielsens Fond, NIH Grant 1R 01 CA 17039, Daell Fonden, Ander Hasselbalchs Fond til Leukæmiens Bekæmpelse, P. Carl Petersens Fond, the Danish Cancer Society, Fonden til Lægevidenskabens Fremme, and the Danish Medical Research Council.

Received 5/31/77. Accepted 8/30/77.