Selective cytotoxicity of phospholipids and diacylglycerols to rat 3Y1 fibroblasts transformed by adenovirus type 12 or its E1A gene.
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 micrograms/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 micrograms/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.
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002472:Cell Transformation, Viral; D004075:Diglycerides / Q000633:toxicity*; D005230:Fatty Acids, Nonesterified / Q000633:toxicity; D005989:Glycerides / Q000633:toxicity*; D008081:Liposomes; D008244:Lysophosphatidylcholines / Q000633:toxicity; D009856:Oncogene Proteins, Viral; D010713:Phosphatidylcholines / Q000633:toxicity; D010743:Phospholipids / Q000633:toxicity*; D013329:Structure-Activity Relationship
D017456:Adenovirus Early Proteins; D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D005989:Glycerides; D008081:Liposomes; D008244:Lysophosphatidylcholines; D009856:Oncogene Proteins, Viral; D010713:Phosphatidylcholines; D010743:Phospholipids