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Last modified on: Monday, July 31, 2000
Copyright © 1994-2008, Information Ventures, Inc.

SPONTANEOUS AND NITROSOUREA-INDUCED PRIMARY TUMORS OF THE CENTRAL NERVOUS SYSTEM IN FISCHER 344 RATS CHRONICALLY EXPOSED TO 836 MHz MODULATED MICROWAVES.
(Eng.) Adey, W. R.; Byus, C. V.; Cain, C. D.; Higgins, R. J.; Jones, R. A.; Kean, C. J.; Kuster, N.; MacMurray, A.; Stagg, R. B.; Zimmerman, G.; Phillips, J. L.; Haggren, W. [Dept. of Biochemistry, Univ. of California, Riverside, CA 92521 (W.R.A., C.V.B. C.D.C.); Univ. of California, Davis, CA 95616 (R.J.H.); Pettis Veterans Affairs Medical Center, Loma Linda, CA 92357 (R.A.J., C.J.K., A.M., R.B.S., J.L.P., W.H.); Swiss Federal Inst. of Technology (N.K.); Loma Linda Univ. Sch. of Allied Health Professions, Loma Linda, CA 92350 (G.Z.)] Radiat Res 152(3):293-302; 1999
Funding: Motorola Corp.


The authors examined the effects of chronic exposure to modulated 836-MHz modulated microwave radiation on the incidence of spontaneous and n-ethyl-N-nitrosurea (ENU-) induced primary central nervous system (CNS) tumors in a rat model. The purpose of the study was to determine if microwave radiation characteristic of a Time Division Multiple Access (TDMA) cellular phone (digital wireless communications) system could act as a neurocarcinogen. Thirty six pregnant Fischer-344 rats were injected iv with 0 or 4 mg/kg ENU on gestational day (GD) 18. This ENU dose was calculated to produce a 15% brain tumor incidence over the lifetime of the offspring and its administration on GD 18 was expected to produce an optimal number of CNS tumors and a minimal number of peripheral nervous system tumors. The dams were exposed or sham exposed while in their cages (far-field exposure) to 836.55-MHz TDMA-type radiation for 2 hr/day starting on GD 19 until delivery, which occurred 2 or 3 days later. Thereafter, exposure of the dams and offspring (2 males or 3 females per cage) in the far field continued until the pups were 21 days old for a total of 25 exposures. When 33 days old, the offspring were irradiated or sham irradiated in the near field for the next 22 mo, until they were approximately 2 yr old. Irradiation was for 2 hr day, 4 days/wk. Rats that survived until the end of the study had a total of 376 near field exposures. The far field exposure component utilized an approximately plane wave produced by a large tapered horn (4.2 inches long with a 4-m2 aperture) that opened into a 2.5-m square, 1.5-m deep target chamber lined with microwave-absorbing foam to minimize reflections. The animals' cages were positioned in a vertically oriented 3 x 3 matrix at the horn aperture, with a normal amount of bedding in each cage, but no food or water. Sham irradiations were performed in a square chamber of identical dimensions. Near-field exposure utilized a carousel system in which 12 exposure platforms, containing 10 rats housed individually in carousels on each platform, were arrayed radially around a central antenna. The antennas were standard Motorola plastic encapsulated half wave sleeved dipoles that were powered by a Motorola TDMA transmitter driving a 200-W linear power amplifier. Each carousel was separated from its neighbors by a distance of 1.7 m. A tubular polyvinyl chloride restraint confined each rat in its carousel for the duration of exposure. Each 2-hr exposure period was divided into 8 cycles of 7.5 min each when the field was alternately on and off. This sequencing was performed by a small computer. The air temperature in the exposure room was maintained at 22 C. A ducted forced air system provided each carousel with an average flow rate of 22.9 l/min. Ambient ELF magnetic fields, measured at each carousel immediately above each antenna and as close as possible to the rats' heads, ranged from below 0.01 (0.1 mG) to 0.04 uT rms in the exposure room, and from 0.02 to 0.025 uT in the sham exposure room. Ambient static magnetic fields in the exposure room and sham exposure room varied from 36 to 39 and from 31 to 34 uT, respectively. SARs were chosen to simulate localized peak brain exposures produced by a TDMA cellular phone. Calculated SARs in the brain based on thermographic images of a rat-shaped model filled with simulated muscle tissue varied from 1.1 to 1.6 W/kg for animals of 150-450 g body weight (respectively) for a 30-mm nose to antenna spacing, and from 0.74 to 1.2 W/kg for a 45-mm nose to antenna spacing over the same weight range. Measurements made in rat cadavers at a 45-mm nose to antenna spacing indicated brain SARs of 1.8 W/kg for a 250-g rat, and 2.3 W/kg for a 450-g rat. A mathematical model, based on finite-difference time-domain and finite integration technique computer simulations and developed using magnetic resonance rat images, was also used to assess dosimetry. The model was tested against measurements made in rat cadavers using fine E-field probes and agreement was better than 10%, within the level of uncertainty in the numerical model. The rats were observed clinically on a daily basis and were weighed weekly. They were evaluated continuously by the staff veterinarian who applied predetermined criteria to decide if and when they should be terminated. These criteria included progressive weight loss, head tilting, ocular discharge, seizures, circling, paresis or paralysis, or any sudden behavioral changes. The veterinarian and pathologist were blind to the animals' treatment status. Pathological surveillance using sentinel animals bred and housed with the experimental rats was also performed during the study: two rats (one male and one female) were necropsied at 3-mo intervals and evaluated for parasitic infestation and serum chemistry determinations. Rats that survived to the end of the experiment were necropsied, the necropsy focusing on CNS tumors. The data were tested statistically by Kaplan-Meier statistics (for survival analysis), the Z-statistic, the chi-squared test, and the t-test. A total of 182 rats of the original group of 236 animals survived to the end of the 2-yr study and were necropsied at 709-712 days. When all data were combined together, the number of CNS tumors found in the microwave-irradiated animals never exceeded those in the sham-exposed control group. This finding clearly indicated that exposure to TDMA-like microwave radiation did not lead to an increase in either spontaneous or ENU induced tumors. The expected incidence of large granulocytic leukemia (LGL) and pituitary adenomas, diseases endogenous to Fischer 344 rats, was observed. LGL was detected in 39 of the 236 rats. There was, however, no evidence of a differential incidence of LGL that could be attributed to separate or combined exposure to ENU or TDMA radiation. Survival of rats exhibiting spontaneous or ENU-induced CNS tumors showed no effect of TDMA radiation exposure. Twenty four glial tumors were detected in 23 animals. No TDMA radiation-mediated increase in spontaneous or ENU CNS tumor incidence was indicated by CNS glial cell tumor incidences of 11.7% (sham/sham - no ENU or microwave irradiation), 3.3% (sham/field), 16.7% (ENU/sham), and 7.1% (ENU/field). Based on the cumulative incidence of brain and spinal cord tumors at the end of the experiment, TDMA-irradiated animals appeared to have a reduced incidence of spontaneous glial tumors, 2 vs. 7 tumors, and ENU-induced glial tumors, 4 vs. 10, but these differences were not statistically significant (p<0.16). In comparing the relative size of CNS tumors in rats that survived to the end of the experiment, 4 microtumors and 3 tumors occurred in the sham/sham group, 1 microtumor and 1 tumor occurred in the sham/field, 6 microtumors and 5 tumors occurred in the ENU/sham, and 4 microtumors occurred in the ENU/field group. Of the rats that died before the end of the study, 13 deaths occurred in the sham/sham group, 9 in the sham/field group 20 in the ENU/sham group, and 12 deaths occurred in the ENU/field group. Of these, 10 deaths in toto were from CNS tumors (2,1,7, and 0, in the 4 groups, respectively). The difference in ENU-induced tumor mortality between ENU/sham and ENU/field groups (the "protective" effect of microwave exposure) was statistically significant, p<0.003. In comparing the relative size of tumors in the premature death groups, there were 4 tumors and 3 microtumors in the ENU/sham group, 1 tumor in the sham/field group, 2 tumors and 1 microtumor in the sham/sham group, and no tumors in the ENU/field group. The authors conclude that the results do not point to an increase in tumorigenesis in the mammalian CNS resulting from exposure to TDMA cellular phone signals at the levels used. The authors note a somewhat higher incidence of spontaneous CNS tumors (11.7% compared to 0.77-3.0% for Fischer 344 rats in Natl. Toxicology Program studies) which they attribute to the more careful histologic analysis used in the present study. The authors suggest that the indication of a TDMA-mediated protective effect (inhibition of CNS tumorigenesis) of marginal statistical significance should be followed up with additional research to validate the observation and clarify the dose-response relationship, dependence of the interaction on developmental stage during exposure, and effects with different levels of neurocarcinogenic agents. (52 Refs). [Copyright 2000, Information Ventures, Inc.]


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