Abstract
The generation of hydrogen peroxide (H2O2) and the derivative free hydroxyl radical (. OH) in cultures of mouse cells grown in the presence of visible light and ambient oxygen was shown previously to be implicated in chromatid damage. Furthermore, chromosome alterations appear to be associated with the spontaneous neoplastic transformation of mouse cells in culture. An attempt was made in this study to reduce the incidence of chromosomal aberrations and delay or prevent the onset of spontaneous neoplastic transformation of freshly isolated mouse cells, both fibroblasts and epidermal keratinocytes, by adding catalase to the culture medium, shielding the cultures from wavelengths less than 500 nm and providing a gas phase of 0-1% O2. These conditions significantly decreased the incidence of chromosomal aberrations in both cell types, and in fibroblasts prevented tumourigenicity in non-irradiated syngeneic mice, and increased latent periods for tumour development in X-irradiated mice. The epidermal keratinocytes were particularly resistant to spontaneous neoplastic transformation under all conditions tested. These observations on the protective effect of extracellular catalase suggest that H2O2, a normal metabolite, and/or the derivative .OH can directly or indirectly produce genetic damage and neoplastic transformation in mouse fibroblasts.
Highlights
The introduction of banding techniques for the analysis of chromosomes with recent developments in molecular biology has revealed chromosome aberrations in most human neoplasms and nonrandom translocations in certain mouse and human tumours that appear to activate cellular oncogenes (Land et al, 1983; Potter et al, 1984; Yunis, 1983). Chromosomal aberrations such as translocations, deletions and duplications may play a role in the spontaneous neoplastic transformation of rodent cells in culture
The transformed cells grow as malignant neoplasms when implanted in syngeneic or compatible hosts
Cultures were carried in Pyrex T-15 flasks in 3 ml Dulbecco's modified Eagle's medium (DMEM, MA Bioproducts, Walkersville, MD) supplemented with 10% foetal bovine serum (Flow Laboratories, Inc., McLean, VA, USA)
Summary
The introduction of banding techniques for the analysis of chromosomes with recent developments in molecular biology has revealed chromosome aberrations in most human neoplasms and nonrandom translocations in certain mouse and human tumours that appear to activate cellular oncogenes (Land et al, 1983; Potter et al, 1984; Yunis, 1983). Chromosomal aberrations such as translocations, deletions and duplications may play a role in the spontaneous neoplastic transformation of rodent cells in culture. Though rare, have been reported in human cells (Mukherji et al, 1984; Nakagomi & Ishida, 1980)
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