Transformation of C3H 10T1/2 cells by low doses of ionising radiation: a collaborative study by six European laboratories strongly supporting a linear dose-response relationship.
For the assessment of radiation risk at low doses, it is presumed that the shape of the low-dose-response curve in humans for cancer induction is linear. Epidemiological data alone are unlikely to ever have the statistical power needed to confirm this assumption. Another approach is to use oncogenic transformation in vitro as a surrogate for carcinogenesis in vivo. In mid-1990, six European laboratories initiated such an approach using C3H 10T1/2 mouse cells. Rigid standardisation procedures were established followed by collaborative measurements of transformation down to absorbed doses of 0.25 Gy of x-radiation resulting in a total of 759 transformed foci. The results clearly support a linear dose-response relationship for cell transformation in vitro with no evidence for a threshold dose or for an enhanced, supralinear response at doses approximately 200-300 mGy. For radiological protection this represents a large dose, and the limitations of this approach are apparent. Only by understanding the fundamental mechanisms involved in radiation carcinogenesis will further knowledge concerning the effects of low doses become available. These results will, however, help validate new biologically based models of radiation cancer risk thus providing increased confidence in the estimation of cancer risk at low doses.
Mill
A J
AJ
Faculty of Applied Sciences, University of the West of England, Bristol, UK. aj-mill@uwe.ac.uk
Frankenberg
D
D
Bettega
D
D
Hieber
L
L
Saran
A
A
Allen
L A
LA
Calzolari
P
P
Frankenberg-Schwager
M
M
Lehane
M M
MM
Morgan
G R
GR
Pariset
L
L
Pazzaglia
S
S
Roberts
C J
CJ
Tallone
L
L
D000818:Animals; D001681:Biological Assay / Q000592:standards; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005060:Europe; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D009381:Neoplasms, Radiation-Induced; D011835:Radiation Protection; D018570:Risk Assessment