Summary We have carried out a series of experiments to compare the response to radiation and drugs of cells disaggregated from solid tumours as assayed by clonogenic survival and by an isotope incorporation method. This latter assay consisted of measuring the 24h uptake of tritium labelled thymidine into cells plated in liquid medium upon a layer of semi-solid agar. The isotope was administered 4 days after plating. For cells from the RIF-1 mouse tumour, good agreement was seen between response to radiation, adriamycin, vincristine and CCNU as measured by the two assays. The two curves for radiation response, for example, showed similar shoulders and subsequent exponential regions. For cells from xenografts of the NCI-H69 human small cell lung cancer line, the response to radiation was dose-related for both assays, but the curve for clonogenic assay was about twice as steep as that for isotope uptake. For a range of five cytotoxic drugs, good agrement was seen between the two assays over the first 1N decades of response but with a tendency for the isotope uptake curve to plateau with further increasing drug dose.It appears that, at least for these two well-defined experimental tumour systems, the isotope uptake assay can provide a rapid quantitative assessment of cellular drug and radiation sensitivity comparable to that provided by clonogenic assay but in a much shorter period of time.
We have carried out a comparison of two different methods for cloning human lung cancer cells. The method of Courtenay & Mills (1978) generally gave higher plating efficiencies (PE) than the method of Carney et al. (1980). The number of colonies increased with incubation time in both methods and the weekly medium replenishment in the Courtenay method was advantageous for longer incubation times of several weeks. In the Courtenay method, the use of August rat red blood cells (RBC) and low oxygen tension were both found to be necessary factors for maximum plating efficiency. The usefulness of heavily irradiated feeder cells in improving PE is less certain; each cell type may have its own requirement.
A B S T R A C T Vitamin K3 inhibits the conversion of benzo(a)pyrene to its more polar metabolites in an in vitro rat liver microsomal system. Vitamin K3 also inhibits benzo(a)pyrene metabolism in rat liver fragments and reduces its mutagenicity in the Ames test. Higher concentrations of vitamin K3 are required to comparably reduce benzo(a)pyrene metabolism when the microsomal system has been induced with 3-methylcholanthrene. High pressure liquid chromatography analysis of the products of benzo(a)pyrene metabolism shows a uniform reduction of all the metabolic products. When tumors were induced in ICR/Ha female mice by the intraperitoneal injection of benzo(a)pyrene, those mice given vitamin K3 before or both before and after benzo(a)pyrene had a slower rate of tumor appearance and tumor death rate as compared with those receiving benzo(a)pyrene alone. However, vitamin K, increased the rate of tumor death while vitamin K deprivation and warfarin decreased the rate of tumor appearance and death in benzo(a)pyrene-injected mice.These studies indicate that vitamin K3 is an inhibitor of aryl hydrocarbon hydroxylase and reduces the carcinogenic and mutagenic metabolites in vitro, and inhibits benzo(a)pyrene tumorigenesis in vivo. That vitamin K, enhances the benzo(a)pyrene effect while warfarin and vitamin K deficiency inhibit benzo(a)pyrene tumorigenesis indicates that vitamin K1, vitamin K deprivation, or possibly blockade of its metabolic cycle also modulates benzo(a)pyrene metabolism in vivo but by a mechanism or at a site different from the vitamin K3 effect. The vitamin K series should be considered as capable of serving a regulatory func-
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