Mitogenic signal transduction: a common target for oncogenes that induce resistance to ionizing radiations.
We hypothesized that resistance to ionizing radiations accompanying neoplastic transformation caused by some oncogenes was due to common biochemical pathways affecting the mechanism of mitogenic signal transduction. In order to verify this hypothesis, we studied the formation of mitogenic second messengers in cells transformed by oncogenes that induce radioresistance. We observed an increase of diacylglycerol which activates protein kinase C, an increase of phosphatidylcholine metabolism, with a concomitant decrease of inositol lipid metabolism. Our data show that sensitivity to ionizing radiations was inversely related to the intracellular level of diacylglycerol; study of signalling alterations in spontaneous tumors could provide predictive indications about the responsiveness of neoplasia to radiation therapy.
Ruggiero
M
M
Lab. of Mol. Biol., Univ. of Firenze, Italy.
Casamassima
F
F
Magnelli
L
L
Pacini
S
S
Pierce
J H
JH
Greenberger
J S
JS
Chiarugi
V P
VP
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004075:Diglycerides / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D051379:Mice; D009857:Oncogenes / Q000502:physiology*; D010713:Phosphatidylcholines / Q000378:metabolism; D011836:Radiation Tolerance / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology*
D004075:Diglycerides; D007295:Inositol Phosphates; D010713:Phosphatidylcholines