Myogenic cell proliferation and generation of a reversible tumorigenic phenotype are triggered by preirradiation of the recipient site.
Environmental influences have profound yet reversible effects on the behavior of resident cells. Earlier data have indicated that the amount of muscle formed from implanted myogenic cells is greatly augmented by prior irradiation (18 Gy) of the host mouse muscle. Here we confirm this phenomenon, showing that it varies between host mouse strains. However, it is unclear whether it is due to secretion of proliferative factors or reduction of antiproliferative agents. To investigate this further, we have exploited the observation that the immortal myogenic C2 C12 cell line forms tumors far more rapidly in irradiated than in nonirradiated host muscle. We show that the effect of preirradiation on tumor formation is persistent and dose dependent. However, C2 C12 cells are not irreversibly compelled to form undifferentiated tumor cells by the irradiated muscle environment and are still capable of forming large amounts of muscle when reimplanted into a nonirradiated muscle. In a clonal analysis of this effect, we discovered that C2 C12 cells have a bimodal propensity to form tumors; some clones form no tumors even after extensive periods in irradiated graft sites, whereas others rapidly form extensive tumors. This illustrates the subtle interplay between the phenotype of implanted cells and the factors in the muscle environment.
Morgan
Jennifer E
JE
Muscle Cell Biology Group, Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College School of Technology and Medicine, London W12 0NN, UK. jmorgan@csc.mrc.ac.uk
Gross
Jacqueline G
JG
Pagel
Charles N
CN
Beauchamp
Jonathan R
JR
Fassati
Ariberto
A
Thrasher
Adrian J
AJ
Di Santo
James P
JP
Fisher
Ivan B
IB
Shiwen
Xu
X
Abraham
David J
DJ
Partridge
Terence A
TA
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology / Q000528:radiation effects*; D002455:Cell Division / Q000502:physiology / Q000528:radiation effects*; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics; D006085:Graft Survival / Q000502:physiology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development / Q000528:radiation effects*; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D012038:Regeneration / Q000502:physiology / Q000528:radiation effects*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D016378:Tissue Transplantation
D016189:Dystrophin