Cellular transformation by radiation: Induction, promotion, and inhibition
- 1 January 1981
- journal article
- review article
- Published by Wiley in Journal of Supramolecular Structure and Cellular Biochemistry
- Vol. 16 (4), 311-336
- https://doi.org/10.1002/jsscb.1981.380160403
Abstract
Mammalian cell cultures offer powerful tools for evaluating qualitatively and quantitatively the oncogenic potential of radiation over a wide range of doses with particular importance at the low dose range that is relevant to human exposure and risk. Our studies have shown that early events in the process of radiation induced transformation in both rodent and human cells requires initial replication for fixation of transformation as a hereditary property of the cells and further clonal expansion for full expression. Early events (fixation) are inhibited by cell–cell contact and high cell density but can be modified at low temperature where repair processes are slowed. Cell–cell contact and communication in tissue organization may be in part responsible for our findings that radiation oncogenesis induced in utero in hamsters is expressed at a lower frequency than that induced in vitro. Quantitative studies carried out on hamster embryo cells indicate that neutrons are more effective in their carcinogenic potential than x-rays but also more toxic, that splitting the dose of x-rays at low doses leads to enhanced transformation, but that at high doses protracted radiation has a sparing effect. At all dose ranges survival was increased by protracting the radiation dose, thus suggesting that different repair processes must be involved for survival and transformation. Similar observations were seen when the protease inhibitor Antipain was found to enhance transformation in rodent and human cells when present at the time of radiation, but was protective when added after radiation. Survival was not modified under any of those conditions, and Antipain did not affect DNA replication and repair. In our qualitative studies, once cells are transformed by radiation, they exhibit a wide range of structural and functional phenotypic changes, some of which are membrane-associated and are expressed within days after induction. Our current studies on nutritional and hormonal influences on radiation transformation indicate the following: Pyrolysate products from broiled protein foods act in synergism with radiation to produce transformation, whereas vitamin A analogs are powerful, preventive agents. Retinoids inhibit both x-ray-induced transformation and its promotion by TPA: these modifications (enhancement by TPA, inhibition by retinoids) are not reflected in sister chromatid exchanges, but are reflected in the level of membrane associated enzymes Na/K ATPase. Whereas retinoids modify late events (expression, promotion), we find that thyroid hormone plays a crucial role in the early phases of radiation and chemically induced transformation. Under hypothyroid conditions no transformation is observed. The addition of triiodothyronine at physiological levels results in a transformation rate that is dose-related. Our recent success in transforming human skin fibroblasts will enable quantitative and qualitative studies of radiation carcinogenesis in a system relevant to man.Keywords
This publication has 37 references indexed in Scilit:
- Protease inhibitors neither damage DNA nor interfere with DNA repair or replication in human cellsMutation research. Reviews in mutation research, 1981
- The interaction of ionizing radiation and food pyrolysis products in producing oncogenic transformation in vitroCancer Letters, 1981
- Unique transforming gene in carcinogen-transformed mouse cellsNature, 1981
- Thyroid hormone modulation of X ray-induced in vitro neoplastic transformationNature, 1980
- X-ray-induced in vitro Neoplastic transformation of human diploid cellsNature, 1980
- The pattern of disease in the post-infection era: national trendsProceedings of the Royal Society of London. B. Biological Sciences, 1979
- Transformation of Mammalian Cells in vitro by Low Doses of X-raysNature, 1973
- Repair replication in mammalian cells after X-irradiationMutation research. Reviews in mutation research, 1972
- Intercellular communication and tissue growthThe Journal of Membrane Biology, 1969
- In Vitro Cell Transformation by X-IrradiationNature, 1966