Studies have been made on the growth and cell population kinetics of a spontaneous rat mammary fibroadenoma and of 10 successive transplantation passages. The volume doubling time decreased from about 30 days in the primary tumour and first two transplants to 1·7 days in the tenth transplant. This acceleration was accompanied by a considerable shortening of the mitotic cycle and of its S and G1 phases but without change in the proportion of time spent in S. There was also a reduction in the apparent extent of cell loss and a considerable increase in the growth fraction. Histological changes were noted and studies by feulgen densitometry indicated a considerable shift in ploidy from hyperdiploid to hypertetraploid. The results constitute a detailed example of the effect on tumour growth kinetics of serial transplantation. ImagesFig. 5

The effects of local X-irradiation of a solid, rapidly metastasizing sarcoma in the rat on kinetics of dissemination and growth of metastases in lymph nodes and lungs are described. Corresponding dose-effect curves obtained for growth of the primary tumour (Pr) and its metastases in unirradiated tissues showed that local irradiation of Pr caused an exponential decrease in growth of metastases due to any dissemination occurring after irradiation, but was also responsible for stimulating growth of metastases already established before treatment in lymph nodes and in lungs. This stimulating effect was most marked when Pr was larger at the time of treatment and when high doses were given to eradicate Pr. This effect is attributed to the liberation of growth stimulating substances (GSS) from a pool of GSS produced in the irradiated Pr by sterilized, but metabolically active and growing tumour cells (HR cells). This effect of HR cells on tumour growth and metastases was also demonstrated when rats were inoculated with viable tumour cells and subsequently treated by injecting large doses of HR cells prepared in vitro, into tissues remote from the Pr tumour site. The systemic effects of GSS on metastases were most clearly seen after immunosuppression of recipient hosts by sublethal whole body irradiation, since immunosurveillance in unirradiated rats resulting from a rapidly developing allogenic tumour-host incompatibility caused marked reductions in clonogenicity of the tumour which tended to overshadow the GSS effect. The latter was also masked in immunosuppressed hosts when excessively high rates of dissemination were due to growth of large Pr inocula for sufficiently long to “saturate” the capacity for growth of metastatic tumour in lymph nodes and lungs. The relevance of these findings to clinical radiotherapy is discussed.

The distribution of 3H-chlorambucil following its administration by subcutaneous injection to Yoshida ascites tumour-bearing rats has been examined, in an attempt to elucidate the metabolic fate and mode of action of this drug. Drug uptake into the body tissue was rapid, with a high level of radioactivity being associated with the plasma and ascitic fluid during the initial 6-hour period after treatment. Previous studies in vitro had shown that chlorambucil-resistant cells accumulated less drug than their sensitive counterparts: this discrepancy was also observed after in vivo drug treatment and was reflected in the two-fold difference in extent of binding of tritium to DNA, RNA and protein isolated from the 2 cell strains. These results might in part explain the observed difference in metabolism of chlorambucil by the resistant and sensitive strain of Yoshida ascites sarcoma cells.

Estimates are presented of the median potential cell population doubling time in five neuroblastomas and six nephroblastomas. The median time in the neuroblastomas was 4·2 days (101 hours) and in the nephroblastomas was 7·8 days (188 hours). Estimates of the duration of metaphase in the two kinds of tumour are also offered, based on the natural mitotic index in six neuroblastomas and five nephroblastomas. The findings are set in the context of a brief review of other studies on the cell population kinetics of human tumours. A more detailed but frankly speculative analysis is made of one nephroblastoma which suggests that cells are produced at the rate of at least 5 per 1000 tumour cells per hour, of which about 3 are lost.

The results are presented of the examination of 28 neoplasms from the nervous system for an organ-specific antigenic material demonstrated in glial cells and myelin, using gel diffusion, immunocytotoxicity and immunofluorescence techniques. The antigenic material was demonstrable in benign gliomas and in those of low-grade malignancy, but not in the more malignant gliomas and non-gliomatous neoplasia. The implications of the loss of specific antigenic material with reference to cell structure and function, and some fallacies in the interpretation of the significance of tissue specific antigen in carcinogenesis are discussed. ImagesFigs. 1-4Figs. 5-7Figs. 8-11

The response to 5, 10, 20 or 40 weekly paintings with DMBA of the dorsal and vulval skin in intact and castrate rats is compared. Squamous and basal celled tumours appear faster in the dorsal than the vulval region with 5, 10, or 20 paintings, but at the same rate with 40 doses. The rate of induction of epithelial tumours is optimal with 20 applications dorsally, but increases with dose at the vulva. Progression of malignancy of squamous celled tumours is greater and faster in the dorsal than in the vulval region. For basal celled neoplasms of the vulva there is a peak value in malignant conversion at 20 doses, but otherwise there is no consistent difference in the pattern at the two sites. Castration reduces the incidence of basal celled tumours of the vulva in rats painted weekly for life, but does not affect the incidence of epithelial tumours of the skin. Sarcomas occur in 29% of rats in the dorsal region, but in only 0·4% at the vulva. Sarcomatous changes in the stroma of epitheliomas are also more frequent in the dorsal skin. Local factors rather than variation in individual sensitivity account for the differences with region in the carcinogenic response as shown by their persistence in rats treated simultaneously at both sites. ImagesFig. 11Fig. 12Fig 13Fig 14

The rat Walker 256 tumour was grown in mice that had previously been thymectomized and treated with anti-lymphocyte serum. These rat tumour-bearing mice were used to determine the therapeutic indices of 4 anti-tumour drugs. The agent with the highest index of the four examined was 5-aziridino 2,4-dinitrobenzamide (CB1954), followed by melphalan, aniline mustard and methotrexate, in that order. This rank order is the same as that found when therapeutic indices are determined on the Walker tumour growing in the rat. In this system, therefore, drugs have been ranked correctly in effectiveness against a rat tumour by measuring their effects on the tumour when growing in an immunosuppressed xenogeneic species. The implications for testing the drug sensitivity of individual human tumours before treating the patient are discussed.

An epidemiological study of 1504 cases of leukoplakia seen at the Tata Memorial Hospital, Bombay, indicates that the oral cavity was the site of the disease in 95% of the cases. The buccal mucosa was the commonest site affected in all religious communities of Western India except among Parsis. Parsis, a majority of whom are non-smokers and non-chewers of tobacco, had leukoplakia more often on the anterior 2/3rd tongue than on the buccal mucosa and this pattern persisted in the distribution of cancer also, whereas people from Gujarat more often smoke; in these the buccal mucosa was commonly affected with leukoplakia, but cancer was not so frequent in this site. Statistical computation of the risk of malignant transformation indicates that males have a 4·8 times higher risk of developing cancer when they have leukoplakia than the normal population, and the females have 7 times higher risk of developing cancer in the presence of leukoplakia. It was felt that leukoplakia not associated with smoking habits had a greater chance of malignant transformation.

The 1962-66 cancer mortality of Polish migrants to Australia is compared with the cancer mortality prevailing in Poland and in Australia. Small numbers compel to limit the analysis to the most frequent cancer sites only. The main findings are: (a) Stomach cancer mortality of Polish migrants to Australia is intermediate between the high mortality in Poland and the much lower one in Australia. (b) Intestinal tract and breast cancer mortality of Polish migrants is displaced upwards, from the low Polish level to the much higher Australian one. (c) Lung cancer mortality of Polish male migrants does not differ distinctly from the mortality observed both in the country of origin and of adoption of these migrants. The presented findings are compared with the results of a similar study of Polish migrants to the U.S. Aims for future studies are briefly outlined.

The pleomorphic cytology of the HT-1 cell line is described. Cytochemical studies indicated the presence of glycogen and lysosomes in these cells. Cytogenetic studies demonstrated the presence of a large telocentric chromosome (M1) and two minute chromosomes (M2) not found in normal hamster cells. A cloned line was isolated which did not contain these marker chromosomes. All cells were hyperdiploid with chromosome number around triploidy, although none was a true triploid. Ultrastructural studies revealed the presence of “nuclear bodies”, “dense bodies” and “interchromatinic granules” which have been previously described in viral induced malignancies. A few of the cells contained in their cytoplasm structures of approximately 700 [unk] in diameter which bore some resemblance to immature virus particles. Both light and electron microscopy demonstrated some nuclei lacking chromatin aggregates. This is interpreted to mean that the total genetic material of these nuclei was dispersed as free DNA not linked with histone to form chromatin aggregates. ImagesFig. 9Fig. 12Fig. 16Fig. 13Fig. 17Fig. 14Fig. 18Fig. 19Fig. 1Figs. 2-5Fig. 7Fig. 10Fig. 8Fig. 11Fig. 15