Investigación - Toxicológicos

Utteridge TD, Gebski V, Finnie JW, Vernon-Roberts B, Kuchel TR.

In 1997 Repacholi and his colleagues reported that exposure of mice to radiofrequency (RF) radiation at 900 MHz for 18 months increased the incidence of lymphoma. These authors stated that there was a need to "replicate and extend" their study. Utteridge and co-authors carried out a replication study using the same strain of mice as in Repacholi's - one that is particularly prone to develop lymphoma. They included refinements designed to overcome perceived shortcomings in the original study:

A wide variation in SAR because the mice were unrestrained;
the use of a single-exposure level, which meant that no inference could be drawn about whether a dose-response relationship existed;
the lack of standardized assessment criteria for deciding which mice would be selected for necropsy;
mice selected for necropsy were not replaced with tissue-equivalent phantoms, consequently altering the dosimetry in the remaining mice;
the disposal of the surviving mice without performing necropsies to back the assumption that there were no relevant diseases in those mice.
no normal mice were studied to determine if the effect was unique to the cancer-prone mice

The authors used a double-blind design. A total of 120 heterozygous (lymphoma-prone) and 120 wild-type mice were exposed at each of the exposure levels (SARs 0.25, 1.0, 2.0 and 4.0 W/kg); 120 mice of each strain were sham-exposed; and there were 120 freely moving negative control mice of each strain. Thirty heterozygotes and 30 wild-type mice were used as positive controls by injecting them with ethylnitrosurea and sham-exposing them. One hundred sentinel mice were also used for health monitoring purposes. Hence a total of 1600 mice were used in the study. The mice were exposed to RF radiation at 898.4 MHz or sham-exposed for 1 hour/day, 5 days/week for up to 24 months. The mice were restrained during exposure. The dosimetry was checked independently at regular intervals by staff of the Australian Radiation Protection and Nuclear Safety Agency and the Defence Science Technology Organization. The other shortcomings of the Repacholi study were addressed appropriately.

Utteridge and colleagues found that different types of lymphomas occurred - lymphoblastic lymphomas usually developed before age 10 months, and non-lymphoblastic at more than 10 months. A few other types of tumours were found in a small number of the animals. The tumour incidences were no higher in the exposed mice than in the sham-exposed, either for lymphoma or for total tumour incidence. There was no evidence of a dose-dependent trend. For lymphoblastic lymphoma there was actually a decreased incidence of tumours in the exposed mice, although this reached statistical significance only for the 0.25 W/kg group.

In summary, this study did not confirm the findings of the Repacholi study, in that there was no evidence of an increase in lymphoma incidence after RF-field exposure.

The study was funded by the Australian National Health & Medical Research Council and was carried out at the University of Adelaide.

Addendum (March, 2003): In the February 2003 issue of "Radiation Research", three letters were published that raised concerns about the above paper:

There was an apparent discrepancy in the survival figures quoted in different parts of the paper
Restraint of the mice could have produced stress that might obscure the effect of the exposure
The incidence of lymphoma in sham-exposed mice was 75%, much higher than the 20 - 30% seen in other studies
The variability in size of the mice and in their weight gain could affect the SAR
The animals were exposed for one hour once per day to the radiation, rather than the 30 minutes twice per day in the Repacholi study. This could have altered the effect of the "sleep-wake cycle".

Utteridge and colleagues replied to these concerns.
They do not feel that immobilization stress is a factor since there was no difference in tumour incidence between sham-exposed mice (who were restrained) and cage control mice (who were not). These data were not given in the original paper.
With regard to the main criticism of an apparent discrepancy in survival figures, the authors state that their survival curve used "days of exposure" on the x-axis rather than absolute age. Since the mice were not exposed on weekends or other holidays their survival time appeared shorter, in their original paper, than it actually was. They go on to say that when absolute age is used the survival of their control mice at 18 months is about the same as those in the Repacholi study.
They do not adequately address the comments about time of exposure or SAR values.

Several researchers have said that the use of "days of exposure" rather than "absolute age" in the survival curve is highly unusual, according to "Microwave News" in the January/February 2003 issue.

Other attempts to replicate the Repacholi study are underway at the present time.