Tissue culture and experimental carcinogenesis

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Io assess the risk of cancer development we usually need to extrapolate data from laboratory experiments to the human situation. However, there is a wide variety of both qualitative and quantitative results from studies with different mammalian species. Just a few examples will be mentioned here. Incubations of benzo(a)pyrene with the microsomal preparation from respiratory organs produced predominantly trans-4,5-diol (4,5-dihydro-4,5-dihydroxy-benzo(a)pyrene) in rats and rhesus monkeys, while in Syrian hamsters and humans trans-7,8-diol was produced (COHEN and ASHURST 1983). Polycyclic aromatic hydrocarbons and cigarette smoke i.nduce tumors of the respiratory organs in the pulmonary peripheral region in rats, in the pulmonary hilar region in humans, and in the upper respiratory tract in Syrian hamsters (MOHR and DUNGWORTH 1988). In the respiratory tract cell cultures, a tumor promotor, IPA, enhanced colony formation of rat cells, while it inhibited the colony formation of hamster and human cells (BEEMAN et al. 1987). We should, therefore, recognize such species-dependent variations and try to understand the mechanisms underlying their occurrence to make the extrapolation more accurate. One possible approach for archieving this is to use in vitro cell culture techniques. But these should enable the in vitro circumstances to mimic those in vivo as closely as possible. In this approach interspecies comparisons would have to be made between each target cell type, because the microanatomical charcteristics peculiar to each seem to be so striking and critical from species to species (PLOPPER 1983). In addition, certain specific physiological parameters will be required to monitor whether the selected cell culture conditions are working optimally for the comparison of cells from different species. In this regard we have concentrated on the comparison of fetal Syrian hamster and human pulmonary epithelial cells for their specific in vitro functions, including the capacity to metabolize several polycyclic aromatic hydrocarbons and be transformed to a state of anchorage independency. Before we enter into the rather detailed discussion of our recent findings the following is an outline of the techniques we are using.