The publication by Smith-Roe et al. (2019) describes the genotoxicity analyses of rat and mice tissue samples, which were conducted as part of the life-long bioassay of the U.S. National Toxicology Program (NTP) on behalf of the U.S. Food and Drug Administration (FDA) regarding carcinogenesis of RF-EMF (see BERENIS Newsletter – Special Issue November 2018).
DNA damage was investigated in cells of three brain regions (frontal cortex, hippocampus, and cerebellum), the liver and in leukocytes by the comet assay. Furthermore, chromosomal damage was assessed in red blood cells (immature and mature erythrocytes) by the so-called micronuclei, which detects faulty repair events and/or problems in the DNA replication.
According to the protocol of the NTP study, the animals were exposed to GSM (2G) or CDMA (3G) modulated signals (carrier frequencies, rats: 900 MHz; mice: 1900 MHz) at 10-minute intervals (10 min on, 10 min off) for 18 hours per day and 7 days per week, starting from gestation day 5. This corresponded to a daily cumulative exposure of 9 hours and 10 minutes. After 19 and 14 weeks of exposure for rats and for mice, respectively, tissue samples were collected and refrigerated. For each exposure condition (rats: whole body SAR1 1.5, 3 or 6 W/kg; mice: whole body SAR 2.5, 5 or 10 W/kg), and for both sexes and species, 5 animals were included in the comet assay analysis. Thus, DNA damage data of a total of 800 tissue samples were included.
The authors considered a clear indication of increased DNA damage, when a dose-effect relationship was found as well as a statistically significant difference to control animals (p-value ≤ 0.025). These criteria were met at the highest dose (6 W/kg) in the hippocampus of male rats, in the frontal cortex of male mice after exposure to both signal modulations (10 W/kg), and in the leukocytes of female mice. In addition, some evidence was found in other exposure groups and classified as “equivocal”.
In contrast, no evidence for chromosomal damage was found in any of the exposure groups in the micronucleus assays. It is a well-established concept that induced genome instability results in mutations and thus causes carcinogenesis. Hence, such a study design generally aims to establish a potential causality between tissue-specific DNA damage and increased incidence of tumours.
In this regard, the sex-specific differences found in the cancer and the genotoxicological study of the NTP are remarkable. While little evidence for higher tumour incidence was found in female animals, indications were more frequent in males, especially in rats. The DNA damage observed in brain regions could therefore be related to the increased occurrence of malignant gliomas. However, these ex vivo analyses do not allow for direct conclusions about the causality. DNA damage could be both the cause and the consequence of neoplastic changes as well as non-neoplastic tissue damage.
Notably, the proportion of severely damaged cell nuclei is relatively high, which could indicate extensive tissue damage, but also be due to the methodology used.
Source: BERENIS – The Swiss expert group on electromagnetic fields and non-ionising radiation Newsletter No. 21 / June 2020