A curvilinear dose response of myeloid leukaemia induction in the CBA male mouse was obtained after single whole-body X-irradiation at about 3 months of age. This strain has a very low spontaneous incidence of the disease and no cases were found in the unirradiated controls. The incidence was independent of dose rate over the range used (4.2-552 rad/min). Diagnosis required histopathological examination of various body tissues, the gross anatomical changes being easily confused with other haemopoietic disorders, but a few cases were recognized in life from blood samples. Curve-fitting to various models based on theories of radiocarcinogenic mechanism is described. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5

Many strains of mice from various breeding institutes have natural cytotoxic macrophages. These macrophages can also be present in nude mice, suggesting that this cytotoxicity can be acquired without invovlvement of T cells. The natural cytotoxicity was non-specific for tumour cells, was not sensitive to trypsin treatment, was lost after 5 days incubation, but could be enhanced by foetal bovine serum. The presence of cytotoxic macrophages in the peritoneal cavity was not genetically or age controlled. Natural cytotoxic macrophages did not occur in germ-free mice. The possible causes of natural cytotoxicity are discussed.

In separate experiments, normal foreign tissue and malignant tumour were implanted s.c. into the rat thigh. NMR T1 values of the adjacent normal muscle, resulting from local inflammatory reactions or from malignant invasion, were measured. Elevations in T1 of the underlying muscle occurred within 24 h in both experiments, and it is believed these were caused by rapid inflammatory and immunological reactions to the implants. However the T1 values of muscle samples adjacent to the non-malignant implants decreased during the 11 days after implantation, dropping to values within the normal range. In the second experiment there was progressive malignant invasion into the normal adjacent tissue and the elevated T1 values were maintained throughout the 12-day period. The effects of the implantation on tissue water content are discussed in relation to NMR T1 relaxation times, and the relevance to whole-body NMR imaging of elevated T1 values due to nonmalignant pathological states is considered.

Serum vitamin A concentration were measured in 26 newly diagnosed lung-cancer patients and found to be significantly lower than those of patients of similar age with either non-malignant lung or non-lung diseases. The levels of vitamin A in the lung-cancer patients, but not in the controls, were significantly correlated with serum concentrations of retinol-binding protein (RBP) and zinc. It is suggested that low levels of zinc might reduce the synthesis of RBP and thus reduce the mobilization of vitamin A from the liver.

Direct comparison of skin-tumour induction by 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one (I) and by benzo[a]pyrene on mouse skin, both by repeated application or by initiation with a single dose followed by promotion with croton oil, demonstrated that these two carcinogens have similar potency. After repeated application of (I) the mean latent period for skin-tumour induction was linearly related to the logarithm of the dose over a 10-fold dose range. Under these conditions, application of the aryl-hydrocarbon-hydroxylase inhibitor 7,8-benzoflavone together with (I) inhibited tumour induction by about 40%. By contrast, in the 2-stage experiment, little effect on tumour incidence or latent period was observed when this inhibitor was applied with the single initiating dose of (I). Co-administration of the epoxide-hydratase inhibitor 1,1,1-trichloropropene oxide caused enhancement by shortening the latent period. After s.c. injection of (I) into mice, a similar number of tumours was induced on skin remote from the site of injection by promotion with corton oil begun either one week or 6 months after initiation. Gastric instillation of (I) into female rats induced mammary adenocarcinomas.