Bleomycin-induced lung damage was assessed using both a functional end-point and mortality. The extent of lung damage was found to depend on the schedule, mode of administration and dose of the drug. Greater damage occurred following twice-weekly administration than when the same dose was given as a single injection. Intravenous administration resulted in greater damage than intraperitoneal administration. When bleomycin was given with thoracic irradiation lung damage occurred earlier and at lower radiation doses than with radiation alone. Similar responses were obtained whether bleomycin was given four weeks before, with or four weeks after irradiation. Thus although there was enhanced damage from the combined treatment, there was no evidence of a time-dependent interaction.

No abstract

THE inhibitory effect of a reduction in body weight on tumour genesis and growth in experimental animals has been studied for some years. A reduction in caloric intake has been shown to inhibit the growth of Sarcoma 180 in mice (Bischoff and Long, 1938). Variations in the constituents of the diet have shown that a reduction in fat or protein has no inhibitory effect, and variations in vitamin content have produced a diversity of results with few instances of any inhibitory effects. This literature has been comprehensively summarised by Tannenbaum and Silverstone (1953). Complete regressions were rare (Tannenbaum, 1940) and Tannenbaum and Silverstone (1953) stated that underfeeding or caloric restriction did not appear to be a successful means of controlling the growth of tumours. Barvick and Goodson (1954) showed that food restriction for 24 to 48 hour periods produced no significant inhibition of Sarcoma 180, and in mice on total starvation the tumour sizes at death (5 days) were one-third that of the controls.The present study, with a squamous-celled carcinoma in mice, shows a high proportion of regressions resulting from underfeeding, and relates the effect to the degree of differentiation of the tumour. MATERIALS AND METHODSThe tumour used in this study was a homologous squamous-celled carcinoma in RIII strain mice. Sarcoma 37 in RIII strain mice was also used in a few parallel experiments. The mice used in each experiment were inoculated subcutaneously in the right flank with portions about 1 mm3. taken from the cortex of one parent tumour. The transplants became measurable (about 18 mm.2) about seven days after implantation, and were then divided into two groups-each group containing at least ten mice. The control group received water and diet 41* ad lib., the treated group received water ad lib. and a proportion of the estimated normal consumption of diet 41. It was found that 2 g. per day for each female and 3 g. per day for each male mouse resulted in a loss in body weight of from 20 to 25 per cent. This degree of starvation was the maximum attempted in this series of experiments. The mice in both groups were kept four or five to a cage; the individual weight variations were found to be consistent throughout the groups, consequently no attempt was made to use individual cages.* The percentage composition of diet 41 (Bruce, 1950) is as follows: Wholemeal flour 46, ground oats 40, white fish meal 8, dried yeast 1, dried skimmed milk 3, cod-liver oil 1, sodium chloride 1.

No abstract

IT has been shown by Warren and Whipple (1923) that small aliquot doses of X-irradiation administered over periods of up to 5 days, produced the same degree of destruction of the intestinal mucosa of dogs as a single total dose. This summation effect was lost if the intervals were spread over a longer period. In the treatment of breast cancer Cohen (1952) has suggested that it is not possible to improve the therapeutic ratio by prolonged daily fractionations. Quimby and MacComb (1937) have shown that if the total dose and total treatment time are constant, the number of fractions is not important. Du Sault (1956) in a review of the effects of fractionated doses in radiation therapy, has postulated a latent period within which any type of fractionation will produce the same effect as a single total dose. The effect of fractionated doses administered after this period-during the period of recovery-depends on the degree of recovery from the preceding dose.Lamarque and Gary-Bobo (1955) have assessed the effects of variations in the time interval between two equal fractions, on the survival of eggs of Bombyx mori. In this work it was shown that a maximum effect was produced by a single total dose, and this effect decreased progressively when the dose was fractionated with time intervals up to 24 hours; an increase was then shown with time intervals of 2 and 4 days. Heeren (1948) has shown that the reticulocyte count in mice is lowered to a greater degree by continuous than by discontinuous irradiation. In studies on erythema Reisner (1932) showed that the effect of a single dose was greater than that of fractionated doses. Schottelndreyer (1949), also studying erythema, showed that the biological effect of a single irradiation of 631 r was equivalent to 2064 r given in 12 daily fractions. Fogg and Cowing (1953) however, report that fractionated doses of 294 r produce a greater effect on spermatogonia and spermatocytes of mice than a single total dose.The present study was undertaken to examine the effects of fractionated X-irradiation at varying time intervals on the growth of a transplantable tumour in mice. MATERIALS AND METHODThe transplantable tumour used in this study was Sarcoma 37, inoculated into RIII strain mice. This tumour was selected for the regularity of its growth rate, and absence of spontaneous regressions when inoculated into this strain. The tumours for each experiment were obtained by inoculating 1 mm.3 portions, from the cortex of an actively growing parent tumour, subcutaneously into the right flank of female mice. Each experiment consisted of control and treated