Myeloid leukaemia in X-ray irradiated CBA mice

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

“…The experiments originally reported (Major & Mole, 1978) have continued, the number of mice at a given dose being increased and the range of doses enlarged with the aim of providing degrees of freedom sufficient for statistical testing of theoretical models. Myeloid leukaemia was found after each of 9 different X-ray doses in the range 0.25-4.5Gy inclusive (Table I).…”

“…A very similar picture was found with fission dose group was close to that for its contemporary controls (Table 1). The cumulative mortality curve after 6.0 Gy and in unirradiated controls is illustrated in Major & Mole (1978).…”

“…The macroscopic appearance of AML in the mouse is usually characteristic or highly suggestive (Major & Mole 1978). The spleen is enlarged uniformly 5-20 fold.…”

“…Its scientific basis was not mere empiricism but an assumed analogy between induction of malignant disease and of genetic mutation. This assumption of linearity for radiation leukaemogenesis can now be checked by direct experiment since it has proved possible to induce acute myeloid leukaemia (AML) systematically in an experimental animal by a variety of ionizing radiations, X-rays (Major & Mole 1978, Mole & Meldrum 1981, y-rays (Mole & Major 1983) and fission neutrons (Mole & Davids 1982). The induction process for X-rays is found to increase not linearly but according to the square of the radiation dose.…”

Initiation and promotion at different ages and doses in 2200 mice. III. Linear extrapolation from high doses may underestimate low-dose tumour risks

“…Mondal & Heidelberger (1970) have shown in vitro that they can "transform" most of a population of cultured mammalian cells with MCA, and and have shown in vitro that they can "initiate" most of a population of cultured mammalian cells with an X-ray dose of 100 rad. Major & Mole (1978) have shown that if mice irradiated with 100 rad are randomized between getting and avoiding a further such dose of X-rays, those which get a further dose are less likely to develop leukaemia, presumably because the second dose kills more preleukaemic cells than it generates. Finally, returning to DMBA on mouse skin, it has been shown that 100 doses of 1 jtg of DMBA, given twice weekly are nmuch more tumorigenic than a single dose of 100 jig (Saffiotti & Shubik, 1956), which again is what would be expected if small doses suffice to initiate almost all the cells which are temporarily at risk of initiation.…”