Growth kinetics of human large bowel cancer growing in immune-deprived mice and some chemotherapeutic observations.

Xenografts of human large bowel cancer have been grown in immune-deprived mice. Studies have been made of their intermitotic time and other proliferative characteristics, and their response to single doses of a number of chemotherapeutic agents has been measured. The indications from this study are that, although the growth rate of xenografts is much faster than that for tumors in man, this is likely to be due largely to a difference in rate of cell loss, and the intermitotic time and growth fraction may not have changed substantially. The spectrum of response to chemotherapeutic agents is in line with clinical experience and, although there are many uncertainties and problems still to be resolved, it is indicated that xenografts could provide a useful experimental system for the laboratory study of the chemotherapy of large bowel cancer.

Regenerative response of the rat tracheal epithelium after acute exposure to tobacco smoke: a quantitative study.

The regenerative response of the rat tracheobronchial epithelium after acute exposure to tobacco smoke was studied. Cigarettes were smoked automatically, and the smoke was diluted with air before being inhaled by the animals. Twenty-four hours after the animals were subjected to tobacco smoke, and with vinblastine as a metaphase-arrest agent, a wave of cell proliferation occurred. The intensity of the response was related to the type of smoke (it was more severe for cigarette than cigar tobacco) and depended on the concentration of smoke, but the timing of the response after moderate exposure was constant. The wave of proliferation would appear to be a local response to cell loss or damage, though morphologically the observed changes were slight. With repeated daily exposure, some adaptation of the tissue was apparent, in that the wave of rapid cell reproduction did not recur, but this did not imply that there was no progression of effect with respect to other pathologic processes. The responses to tobacco smoke and sulfur dioxide were compared. Cell proliferation provided a useful and rapid test of certain irritant effects of different types of tobacco smoke, but it was essential that animals free of chronic respiratory disease be used.

The effect of continuous irradiation on cell proliferation and maturation in small intestinal epithelium.

Autoradiographic studies and scintillation counting of crypt material after pulse labelling with 3H-thymidine showed that during continuous irradiation with 290 rads/day a reduced proliferative activity is present in the crypts of rat small intestine after 1 day of irradiation and of normal activity during the remaining period (5 days) irradiation. After cessation of irradiation an increase in proliferative activity can be observed after 1 day of recovery. From the time (36-48 hr after starting of the irradiation) that the number of villus cells is reduced an expansion of the proliferation zone in the crypt was observed. Both effects last until 1 day of recovery after cessation of irradiation. The process of crypt cell maturation and of villus cell function has also been studied during and after continuous irradiation by micro-chemical enzyme analyses in isolated crypts and villi. It was found that the expansion of the proliferation zone in the crypt is accompanied by a decrease in activity of only those enzymes (i.e. non-specific esterases) which normally become active during crypt cell maturation. The activity of enzymes normally present mainly in the functional villus cells remained relatively unaffected by changes in crypt cell kinetics. A hypothesis of different regulation mechanisms of the proliferative activity in the intestinal crypt and a possible explanation of the different behaviour of various enzyme activities as a result of changes in crypt cell proliferation is discussed.

The effect of various cytotoxic agents on bone marrow progenitor cells as measured by diffusion chamber assays.

Two diffusion chamber assays, termed the 'Full" chamber technique and the 'Empty' chamber technique, have been used to determine the effect of various doses of cyclophosphamide, vinblastine and busulphan on the population of diffusion chamber progenitor cells (DCPC). The diffusion chamber dose-response curves were compared to the progenitor cell survivals estimated by the spleen colony technique. The in vitro agar colony assay was also performed on the busulphan-treated marrow. The diffusion chamber and spleen colony techniques estimated similar survivals after cyclophosphamide and vinblastine treatment. However, with busulphan, the chamber, spleen colony and agar colony methods estimated different survivals. The indication is that the diffusion chamber techniques assay the same population of cells as the spleen colony technique, and that busulphan alters the capacity of surviving DCPC to generate granulocytes and macrophages.