Mini reviewAnimal and cellular studies on carcinogenic effects of low frequency (50/60-Hz) magnetic fields1
Introduction
A number of epidemiological studies have suggested an increased risk for cancers, particularly leukemia and brain and breast cancer, with residential or occupational exposure to extremely low frequency (i.e. 50- or 60-Hz) magnetic fields (MFs) such as associated with the generation, distribution and utilization of electric power (cf. Davis et al., 1992; Sagan, 1992; Stevens et al., 1992; Savitz and Ahlbom, 1994). However, the recent report of the National Research Council, National Academy of Sciences (1997)concluded that the results from such epidemiological studies have been inconsistent and contradictory and do not constitute reliable evidence of an association between MF exposure and some forms of cancer. In view of the methodological problems of epidemiological studies on associations between exposures to 50/60-Hz MFs and increased incidence of cancers, laboratory studies are necessary to determine a link, if any, between such fields and carcinogenesis. The majority of laboratory studies have indicated that non-ionizing radiation has no mutagenic effect, i.e. does not initiate cancer (McCann et al., 1993; Murphy et al., 1993). Thus, if 50/60-Hz MF are truly associated with an increased risk of cancer, then these fields must act as a promoter or co-promoter of cancer in cells that have already been initiated. Many cellular studies support this view since MFs are observed to influence enzyme action, signal transduction, protein synthesis/gene expression, discussed below, and these activities play an important role in regulating cell growth and processes important to promotion. Furthermore, some studies have suggested that the genotoxic potential of certain chemical mutagens or ionizing radiation may be affected by co-exposure to MF (McCann et al., 1993).
Section snippets
Processes in carcinogenesis on which 50/60-Hz magnetic fields may act
In the multistage model of carcinogenesis, the three operationally defined stages in tumor formation are initiation, promotion and progression (Fig. 1). Initiation is the interaction of a genotoxic carcinogen (initiator) with the DNA of a cell, resulting in cytogenetic (i.e. DNA) damage that leads to mutation. In addition to initiation by chemical agents or ionizing radiation, the process of initiation is thought to encompass the actions of inherited mutations, cancer-causing viral genes and
In vitro studies on the role of 50/60-Hz magnetic fields in carcinogenesis
As mentioned in the introduction section, and which bears repeating here, is the important concept of MF altering or influencing cellular metabolism and mitogenesis through different pathways of carcinogenesis, involving those that do not involve direct damage to DNA (Fig. 2). Although the precise interaction mechanism(s) for MF is not fully elucidated, on balance, current in vitro laboratory observations are consistent with MF operating, at least in part, through such a non-genotoxic pathway.
Animal studies on the role of 50/60-Hz magnetic fields in carcinogenesis
Animal studies are one of the principal ways of determining toxic and carcinogenic potential of various chemical or physical agents in the environment. In animal studies the variables are rigorously controlled so that the only difference between control and exposure groups is the agent in question. While studies on MF exposure in laboratory animals would be helpful in estimating risks of cancer, until recently only few published reports existed in this respect. In the last 5–6 years, several
Technical and biological factors critically involved in laboratory studies on carcinogenic effects of MF exposure
It is often argued that data from laboratory studies on biological or carcinogenic effects of MF exposure are equivocal or lack independent replication (e.g. Lacy-Hulbert et al., 1995b; Saffer and Thurston, 1995a). In this respect it is important to note that any effect of MF exposure depends on a variety of technical and biological factors, only few of which are known to a sufficient extent (see Table 1). Thus, variation in such technical and biological factors among laboratory studies on
Conclusions
As shown in this review, there is an increasing number of laboratory studies on 50/60-Hz MF exposure which indicate that intermediate MF exposure exerts co-promoting effects in different tumor models. Furthermore, there is some as yet preliminary evidence that chronic (up to lifetime) exposure to high flux density may exert promoting effects on “spontaneous” development of certain tumors. In view of the high tumor incidence found in some animal studies on lifetime MF exposure (Fam and Mikhail,
Acknowledgements
We thank Dr. Meike Mevissen for her help in the literature research.
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This is the last in a series of four papers, the first of which was published in Mutation Res. 387 (1997) pp. 165–171.