Medical/biological study (experimental study)

Indication of cocarcinogenic potential of chronic UMTS-modulated radiofrequency exposure in an ethylnitrosourea mouse model med./bio.

By: Tillmann T, Ernst H, Streckert J, Zhou Y, Taugner F, Hansen V, Dasenbrock C

Published in: Int J Radiat Biol 2010; 86 (7): 529-541

Aim of study (acc. to author)

To study the tumour susceptibility in mice exposed to a UMTS signal for up to 24 months commencing with embryo-fetal exposure.

Background/further details

Animals were exposed to UMTS electromagnetic fields with different intensities (4.8 and 48 W/m²) and the low-dose group (4.8 W/m²) was additionally subjected to prenatal ethylnitrosourea treatment (40 mg ENU/kg body weight).
In total, five treatment groups were used: Two exposure groups, sham exposure group, cage control group and positive control group (ENU treatment only). Exposure and sham exposure of the maternal mice started on day 6 post conception, while the maternal ENU treatment was carried out on day 14 post conception. Each treatment group consisted originally of up to 20 maternal mice and their litters. After the first week of lifetime, litter standardisation was performed and afterwards three female offspring per cage and their mothers were maintained up to the weaning time point. After weaning, maternal mice were removed from the cages and the study was conducted using the three remaining female offspring (thus about 60 mice per group).
Different pre-studies were also performed (e.g. concerning thermoregulation or ENU mortality of a different mouse strain).

Endpoint

cancer: neoplasms and pre-neoplastic lesions and tumour incidences in spleen, kidneys, liver, lung, lymph nodes, and brain

Exposure

- mobile communications
- UMTS

Exposure	Parameters
Exposure 1: 1,966 MHz Exposure duration: continuous for 20 hr/day, 7 days/week for up to 24 months	power density: 4.8 W/m² average over time (deck with low exposure) power density: 48 W/m² average over time (deck with high exposure) SAR: 0.62 W/kg average over mass (whole body) (3 pups (3 g, together with the dam)) SAR: 1.19 W/kg average over mass (whole body) (3 old females (55 g)) SAR: 3.84 W/kg average over mass (whole body) (1 mature female (30 g)) SAR: 4.48 W/kg average over mass (whole body) (1 mature female (30 g, together with 3 pups)) SAR: 5.76 W/kg average over mass (whole body) (3 young females (12.5 g))

Exposure

Parameters

Exposure 1: 1,966 MHz

Exposure duration: continuous for 20 hr/day, 7 days/week for up to 24 months

power density: 4.8 W/m² average over time (deck with low exposure)
power density: 48 W/m² average over time (deck with high exposure)
SAR: 0.62 W/kg average over mass (whole body) (3 pups (3 g, together with the dam))
SAR: 1.19 W/kg average over mass (whole body) (3 old females (55 g))
SAR: 3.84 W/kg average over mass (whole body) (1 mature female (30 g))
SAR: 4.48 W/kg average over mass (whole body) (1 mature female (30 g, together with 3 pups))
SAR: 5.76 W/kg average over mass (whole body) (3 young females (12.5 g))

General information

animals were treated in five groups: i) cage control - no treatment ii) ENU control 40 mg ENU per kg body weight iii) sham exposure iv) UMTS exposure to 4.8 W/m² + 40 mg ENU per kg body weight v) UMTS exposure to 48 W/m²

Exposure 1

Main characteristics

Frequency	1,966 MHz
Type	electromagnetic field
Exposure duration	continuous for 20 hr/day, 7 days/week for up to 24 months

Exposure setup

Exposure source	radial waveguide
Chamber	exposure performed in a three decker exposure device (sham, low and high exposure; see exposure parameters)
Setup	test signal delivered by a generic UMTS signal generator and amplified with a power amplifier
Sham exposure	A sham exposure was conducted.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	4.8 W/m²	average over time	-	-	deck with low exposure
power density	48 W/m²	average over time	-	-	deck with high exposure
SAR	0.62 W/kg	average over mass	calculated	whole body	3 pups (3 g, together with the dam)
SAR	1.19 W/kg	average over mass	calculated	whole body	3 old females (55 g)
SAR	3.84 W/kg	average over mass	calculated	whole body	1 mature female (30 g)
SAR	4.48 W/kg	average over mass	calculated	whole body	1 mature female (30 g, together with 3 pups)
SAR	5.76 W/kg	average over mass	calculated	whole body	3 young females (12.5 g)

Reference articles

Reinhardt T et al. (2007): Exposure set-ups for in vivo experiments using radial waveguides
Ndoumbe Mbonjo Mbonjo H et al. (2004): Generic UMTS test signal for RF bioelectromagnetic studies

Exposed system:

animal
mouse/B6C3F1
whole body

Methods Endpoint/measurement parameters/methodology

cancer: neoplasms and pre-neoplastic lesions (see "morphological/histopathological changes"), tumour incidences, malignancy, multiplicity and metastasising potential in spleen, kidneys, liver, lung, lymph nodes, and brain
morphol./histopathol. changes: complete necropsy (hematoxylin-eosin stain; light microscopy)
health status (serological examinations via sentinel animals), clinical symptoms, morbidity, mortality, body weight

Investigated system:

tissue slices
isolated organ
investigation on living organism

Investigated organ system:

immune system
muscular/skeletal system
respiratory system
brain/CNS
spleen, kidneys, liver, lung, lymph nodes, brain

Time of investigation:

during exposure
after exposure

Main outcome of study (acc. to author)

The high-level UMTS exposure (48 W/m²), the sham exposure, and the cage control groups showed comparable tumour incidences in the organs. In contrast, the ENU-treated and UMTS-co-exposed (at 4.8 W/m²) animals displayed an enhanced lung tumour rate and an increased incidence of lung carcinomas as compared to the controls treated with ENU only. Furthermore, tumour multiplicity of the lung carcinomas was increased and the number of metastasising lung tumours was doubled in the ENU/UMTS co-exposure group as compared to the ENU control group.
The authors conclude that this pilot study indicates a cocarcinogenic effect of lifelong UMTS exposure (4.8 W/m²) in female B6C3F1 offspring subjected to pretreatment with ethylnitrosourea.

Study character:

medical/biological study
experimental study
pilot/exploratory/preliminary study
blind study

Study funded by

Compagnia di San Paolo, Torino, Italy

Replication studies

Lerchl A et al. (2015): Tumor promotion by exposure to radiofrequency electromagnetic fields below exposure limits for humans

Lerchl A et al. (2015): Tumor promotion by exposure to radiofrequency electromagnetic fields below exposure limits for humans
Zeni O et al. (2012): Radiofrequency radiation at 1950 MHz (UMTS) does not affect key cellular endpoints in neuron-like PC12 cells
Lee HJ et al. (2011): Lymphoma development of simultaneously combined exposure to two radiofrequency signals in AKR/J mice
Bartsch H et al. (2010): Effect of chronic exposure to a GSM-like signal (mobile phone) on survival of female Sprague-Dawley rats: Modulatory effects by month of birth and possibly stage of the solar cycle
Hruby R et al. (2008): Study on potential effects of "902-MHz GSM-type Wireless Communication Signals" on DMBA-induced mammary tumours in Sprague-Dawley rats
Sommer AM et al. (2007): Lymphoma Development in Mice Chronically Exposed to UMTS-Modulated Radiofrequency Electromagnetic Fields
Shirai T et al. (2007): Lack of promoting effects of chronic exposure to 1.95-GHz W-CDMA signals for IMT-2000 cellular system on development of N-ethylnitrosourea-induced central nervous system tumors in F344 rats
Zook BC et al. (2006): The effects of pulsed 860 MHz radiofrequency radiation on the promotion of neurogenic tumors in rats
Yu D et al. (2006): Effects of 900 MHz GSM wireless communication signals on DMBA-induced mammary tumors in rats
Huang TQ et al. (2005): Effect of radiofrequency radiation exposure on mouse skin tumorigenesis initiated by 7,12-dimethybenz[alpha]anthracene
Shirai T et al. (2005): Chronic exposure to a 1.439 GHz electromagnetic field used for cellular phones does not promote N-ethylnitrosourea induced central nervous system tumors in F344 rats
Anane R et al. (2003): Effects of GSM-900 microwaves on DMBA-induced mammary gland tumors in female Sprague-Dawley rats
Utteridge TD et al. (2002): Long-term exposure of E-mu-Pim1 transgenic mice to 898.4 MHz microwaves does not increase lymphoma incidence
Bartsch H et al. (2002): Chronic exposure to a GSM-like signal (mobile phone) does not stimulate the development of DMBA-induced mammary tumors in rats: results of three consecutive studies
Zook BC et al. (2001): The effects of 860 MHz radiofrequency radiation on the induction or promotion of brain tumors and other neoplasms in rats
Heikkinen P et al. (2001): Effects of mobile phone radiation on X-ray-induced tumorigenesis in mice
Imaida K et al. (2001): Lack of promotion of 7,12-dimethylbenz[a]anthracene-initiated mouse skin carcinogenesis by 1.5 GHz electromagnetic near fields
Bastide M et al. (2001): Toxicologic study of electromagnetic radiation emitted by television and video display screens and cellular telephones on chickens and mice
Adey WR et al. (1999): Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats chronically exposed to 836 MHz modulated microwaves

Indication of cocarcinogenic potential of chronic UMTS-modulated radiofrequency exposure in an ethylnitrosourea mouse model med./bio.

Aim of study (acc. to author)

Background/further details

Endpoint

Exposure

General information

Exposure 1

Main characteristics

Exposure setup

Parameters

Reference articles

Methods Endpoint/measurement parameters/methodology

Main outcome of study (acc. to author)

Study funded by

Replication studies

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