187.

It is very difficult to see an overall trend for more complex fractiona-

tion patterns.

On different species, treatment schemes involving from 3 to

90 dose fractions administered from 3 days to about 23 weeks have been tested.
Very seldom is the fractionation pattern comparable within each experimental
series, since for the same total dose both the dose per fraction and the total

treatment times are changing.

In some cases [S2, A2, AT, H5, LY, R3] dividing

the dose into smaller and smaller fraction does lead to an increased survival
time following x- or gamma-irradiation. So does the increase in the total
treatment time for the same number and size of fractions.

But in other cases

(M1, K6, M20, C18] a paradoxical effect is observed, i.e., and increase of the
life-shortening upon dose fractionation.

A changing spectrum of the various

diseases contributing to life-shortening with more leukaemia induced at longer

fractionation times has been invoked to explain the oberservations.

The out-

come of a given fractionation treatment depends critically on the characteristics of the biological system as they reflect on the pathology of the animals at
death.

It is difficult therefore to give a numerical value to the effect of frac-

tionation except to say that the effect, when present, is not very large and the
biological variables appear in general more important in determining it, than the
actual change in the dose-time relationships induced by dose fractionation.

188,

Four neutron dose fractionation experiments have also been reported on

mice.

In the first [V1] splitting a dose into 3, 4 or 10 fractions in 3, 4

and 12 days did not result in any significant change in the mean after survival.

The second series [V5] involved changing the number of fractions/week (1,3,6)
for a given weekly dose (60 rad) and a fixed time of treatment (13 weeks) and
was similarly negative.

In the third series [AT] fixed doses (80 and 20 rad

of neutrons) were given singly or subdivided into 24 fractions administered
over 23 weeks and such a scheme produced a significant increase of life-shor-

tening.

Similar observations were also made in the last series [S47].

It

should again be emphasized that the physical parameters of fractionating the
dose are not prevalent over the changes of the pathological expression of the
damage which largely determine the life-shortening effect.

189,

In spite of the absence of a component of wasted radiation that has been

claimed to confound the analysis, the effects of chronic terminated exposures

reviewed in paragraphs 173-180 are more difficult to evaluate than the experiments involving duration-of-life exposure.

In principle, for any given type of

radiation, the effect to be expected should lie between the dose effect re-

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