Ionizing radiation as a carcinogen: practical questions and academic pursuits

Abstract

Cancer is naturally very common, and practical questions about the possibility of radiation-induced harm are often questions about what in other contexts would be called background noise. Central to the question of whether small radiation exposures are carcinogenic is the effect of antenatal radiography. A comparison of singleton and twin births with radiography rates of 10 and 55 per cent respectively showed that radiography must be the main cause of the elevated frequency of malignant disease. In Japanese bomb survivors, most radiation-induced cancer has been found in those irradiated in adult life, less in those irradiated in childhood and adolescence, and least for exposure in utero. Specific biological differences between different kinds of malignant disease in their induction by ionizing radiation are becoming increasingly evident. When dose-response relationships for observed cancer frequencies are to be used as evidence about dose-response relationships for cancer induction, it will always be necessary to allow for the concomitant cell sterilization. When this is done, there is little support for linearity as the method of extrapolation when making predictions about possible effects of low doses but the absence of threshold seems scientifically inescapable. In cellular terms, radiation induction of cancer must be a very rare phenomenon, so rare compared with cell sterilization or mutation induction, that the general corpus of radiobiological understanding may be inapplicable.

The dose-response for x-ray induction of myeloid leukaemia in male CBA/H mice

“…This leads directly to the hypothesis (Mole 1975(Mole , 1983 (Mole 1983) is poor for X-rays (P=0.066). Equation (i) is therefore regarded statistically, physically and radic satisfactory fit to the observations.…”

“…If the corresponding probability of transformation per cell for a dose of 0.01 Gy is p, a = ,N where N is the (unknown) number in the individual of those primitive haematopoietic cells potentially transformable into "mother cells" of myeloid leukaemia. Hence p is orders of magnitude smaller than A (Mole, 1975). No corrections have been made for differences according to radiation dose in overall survival of non-leukaemic individuals, differences which, if they existed, might be expected to bias leukaemia frequencies in a dose-dependent manner.…”

“…Competition between induction and loss of cells by inactivation The observed dose-response for any form of malignant disease induced by ionizing radiation must depend on the interaction of 2 processes, cell transformation and inactivation (Gray 1965;Mole, 1975Mole, , 1979aMole, , 1983 The probability of cell transformation per unit absorbed dose of ionizing radiation must be very much smaller than the probability of cell inactivation (Mole, 1975). This leads directly to the hypothesis (Mole 1975(Mole , 1983 (Mole 1983) is poor for X-rays (P=0.066).…”

“…Cellular inactivation prevents the development of overt malignancies which would otherwise follow induction. The quantitative consequences of this interaction were first examined by Gray (1965) and later by Mole (1975Mole ( , 1979aMole ( , 1983. In principle, corresponding interactions need to be taken into account when assessing the quantitative aspects of induction of malignant disease by other agents.…”

Antenatal Irradiation and Childhood Cancer: Causation or Coincidence?

“…The deficiency will increase with dose in proportion to the increasing probability of sterilization of cells which would otherwise have been able to divide and so form a " tumour ". The idea was first applied quantitatively by Gray (1965) and has proved applicable to other experimental data and to observations on cancer frequencies in irradiated human populations (Mole, 1974). When applied to the data on antenatal exposure of human foetuses, the discrepancies outlined above are reduced to acceptable levels.…”