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Selective Cytotoxicity of Phospholipids and Diacylglycerols to Rat 3Y1 Fibroblasts Transformed by Adenovirus Type 12 or Its E1A Gene¹

Department of Virology, Medical Institute of Bioregulation, Kyushu University 69, Fukuoka 812 [H. S., M. O., A. M., T. M., G. K.], and Department of Agricultural Chemistry, The University of Tokyo, Tokyo 113 [K. O.] Japan

The colony-forming ability of rat 3Y1 fibroblasts transformed by adenovirus type 12 (Ad12) was drastically reduced when the cells were cultivated for 18 h in medium augmented with 300 µg/ml of liposomes composed of either phosphatidylcholine (PC) or phosphatidylinositol. In contrast, those of untransformed 3Y1 cells and simian virus 40-transformed and polyomavirus-transformed 3Y1 cells were not. The cytotoxicity of PC liposomes was also observed in 3Y1 cells transformed by plasmid DNA containing Ad12-E1A gene but not in those transformed by adenovirus type 2, Rous avian sarcoma virus, or plasmid DNA carrying v-Ha-ras oncogene. The extensive killing of Ad12-transformed and E1A-transformed 3Y1 cells occurred in liposomes of dioleoyl-PC and of dilinoleoyl PC but not those of dipalmitoyl PC, distearoyl-PC, or diarachidonyl PC, suggesting that the acyl groups of phospholipids play an important role in cytotoxicity. Dilinoleoylglycerol, 60 µg/ml, was also cytotoxic selectively to Ad12-transformed and E1A-transformed 3Y1 cells, although the toxicity of lysophosphatidylcholine or linoleic acid was not specific to these transformants. These results suggest that cell transformation by Ad12 is characterized by a high sensitivity to exogenously administered phospholipids and diacylglycerol that contain oleoyl or linoleoyl acyl groups and that the sensitivity is attributable to the expression of E1A gene of Ad12.

¹ This work was supported in part by Fukuoka Cancer Association.

² To whom requests for reprints should be addressed.

Received 12/17/86. Revised 5/26/87. Revised 10/ 6/87. Accepted 10/19/87.

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