It is widely accepted that moderate levels of nonionizing electric or magnetic fields, for example 50/60 Hz magnetic fields of about 1 mT, are not mutagenic. However, it is not known whether such fields can enhance the action of known mutagens. To explore this question, a stringent experimental protocol, which included blinding and systematic negative controls, was implemented, minimizing the possibility of observer bias or experimental artifacts. As a model system, we chose to measure mutation frequencies induced by 2 Gy gamma rays in the redox-sensitive hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in Chinese hamster ovary cells. We tested whether a 12-h exposure to a 60 Hz sinusoidally oscillating magnetic-flux density (Brms = 0.7 mT) could affect the mutagenic effects of ionizing radiation on the HPRT gene locus. We determined that the magnetic-field exposure induced an approximate 1.8-fold increase in HPRT mutation frequency. Additional experiments at Brms = 0.23 and 0.47 mT revealed that the effect was reduced at lower flux densities. The field exposure did not enhance radiation-induced cytotoxicity or mutation frequencies in cells not exposed to ionizing radiation. These results suggest that moderate-strength, oscillating magnetic fields may act as an enhancer of mutagenesis in mammalian cells.

The thermal and thermochemical survival responses of mammalian cells growing routinely at pH 7.4 are affected by extracellular pH. The cells show an increase in sensitivity when heated at pH values below about pH 7.0. The possibility that this sensitivity at low pH can be modified by maintaining the cells at pH 6.8 ('EP-2' cells) or pH 6.5 ('EP-1' cells) was examined. When Chinese hamster cells (HA-1) were exposed to 42 degrees C at pH 6.5, 6.8 and 7.4, a dramatic increase in sensitivity was seen at pH 6.5. EP-2 cells similarly exposed showed considerably less difference at the three pH values. Variations in survival due to these pH changes were almost eliminated when the EP-1 cells were exposed to 42 degrees C. HA-1 cells tended to develop less thermotolerance rates and did so possibly at a reduced rate at pH 6.8 when compared to pH 7.4; the reduced pH had only a minor effect on the ability of EP-2 cells to develop thermotolerance. The effects of pH adaptation on the pH dependence of drug cytotoxicity at 37 degrees C or at 43 degrees C were also compared. Adaptation also modified drug cytotoxicity except that cell killing by BCNU (as a function of pH) was similar for both HA-1 and EP-2 cells at both temperatures. EP-2 cells were more sensitive to MMS treatment at 43 degrees C and more resistant at 37 degrees C than were HA-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

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Cells exposed to a variety of stresses such as heat or ethanol respond by increasing their rate of synthesis of a set of proteins termed heat shock proteins (HSP). These proteins then appear to offer protection against the stressor and many other insults. The HSP also play important roles in unstressed cells. They are involved in the regulation of the cell cycle and during specific stages in the development of organisms. Exposure to stress during development (e.g., in pupal stages of insects or during gestation in mammals) leads to birth defects that are specific to the timing of the stress. It has been hypothesized that the ill-timed induction of HSP is responsible for this phenomenon. Epidemiological studies in humans have related teratogenic events to maternal exposures to hyperthermia or ethanol during pregnancy. The rate of alcohol-induced birth defects is greatly enhanced by smoking, suggesting a role for nicotine. Nicotine by itself, however, is said not to induce HSP. We hypothesized that nicotine may act as a coinducer (or facilitator) of stress responses. This possibility we tested on three levels: protection against heat (thermotolerance), induction of specific HSP, and binding of the heat shock transcription factor to the heat shock element. Each of these tests showed clearly that nicotine does indeed play such a role. This places nicotine in a novel position; to date, no other coinducers of stress responses have been reported. Our results may offer an explanation for the epidemiological data cited earlier.Stress responses in mammalian cells are characterized by two readily measured events. First, the protein synthesis pattern of the stressed cell is modified. The rates of synthesis of many normal cell proteins are reduced, while the synthesis of a specific set of proteins (and the relevant mRNAs) is either enhanced or induced de novo. These latter proteins are termed stress proteins and are of two types: proteins common to many stresses and proteins specific to the individual inducer (23). The second event is the development, in the surviving cells, of a transient resistance to the stressor; this is frequently accompanied by cross-resistance to other inducers (10, 13, 21). Many investigators have suggested that the stress proteins are responsible for this induced resistance, although direct proof is lacking (20,36).Among the inducers of stress responses are heat shock; exposure to aliphatic alcohols (including ethanol), metals such as cadmium, or sodium arsenite; and release of cells from hypoxia (23). A common feature of these treatments is protein damage. Indeed, several studies have shown that damaged proteins or the intracellular presence of proteins deemed "foreign" by the cell can lead to the induction of a response that is similar to that seen after heat shock (1, 14, 19). The heat shock response has been studied far more extensively than any other stress response. The reasons for this include the current interest in the use of hyperthermia in cancer therapy, the ease of induction of the resp...