PURPOSE: Long-term exposure to extremely low-frequency (60 Hz) electromagnetic fields (ELF-EMF) raises the questions of the induction of biological effects including tumorigenesis. One mechanism through which ELF-MFS could influence neoplastic development is the imbalance of cellular proliferation and cell apoptosis. The present study investigated the effect of ELF-EMF on chemically-induced thyroid carcinogenesis in a rat. METHODS: We examined cellular proliferation index measured by anti-Ki-67 antigen, apoptosis, apoptosis related proteins such as caspase 3 and p53, and cell cycle-related proteins (cyclin D1 and p21(WAF1/Cip1)). Forty Male F344 rats received a subcutaneous N-bis(2-hydroxypropyl)nitrosamine (DHPN, 2,800 mg/kg) injection, and 1 week later were allowed free access to drinking water containing sulfadimethoxine (0.1%) for 12 weeks. Twenty rats were exposed by ELF-EMF. During the carcinogenesis, sequential histological changes from hyperplasia, adenoma, and ultimately to overt carcinomas were noted. RESULTS: The exposure group of ELF-EMF, significantly increases the number size of carcinomas. Also, the proliferative and apoptotic indices were significantly increased in the ELF-EMF exposure group than in the control group. The caspase 3 protein expression did not show any significant changes between ELF-EMF group and control group. The p53 protein was not detected in both ELF-EMF exposure and control group. Among the cell cycle related proteins, cyclin D1, not p21(WAF1/Cip1), was significantly increased in adenomas and carcinomas in ELF-EMF exposure group compared with the control group. CONCLUSION: Exposure of ELF-EMF effects on chemically-induced rat thyroid carcinogenesis as results of altered increase of cellular proliferation, apoptosis, and cyclin D1 expression.
Adenoma ; Animals ; Apoptosis ; Caspase 3 ; Cell Cycle ; Cell Proliferation ; Cell Transformation, Neoplastic ; Cyclin D1 ; Drinking Water ; Electromagnetic Fields ; Humans ; Hyperplasia ; Male ; Nitrosamines ; Proteins ; Rats ; Rats, Inbred F344 ; Sulfadimethoxine ; Thyroid Gland

BACKGROUND AND OBJECTIVES: In neonatal hyperbilirubinemia, accumulation of unconjugated bilirubin in the central auditory pathway and basal ganglia may cause sensorineural hearing loss and neurologic sequelae. The effect of unconjugated bilirubin on the brain is known well through auditory brainstem responses (ABRs). However, there is no evidence of pathologic changes in the cochlea. Jaundiced (jj) Gunn rats have been used as a good animal model for hyperbilirubinemia-related auditory dysfunction. The purpose of this study is to evaluate the bilirubin ototoxicity using ABR and DPOAE in jaundiced Gunn rats before and after sulfadimethoxine injection. MATERIALS AND METHOD: Experiments were conducted on three homozygous (jj) P19 (postnatal 19 days) littermates, one heterozygous Gunn rat, five P21 jj littermates, and one nj Gunn rat littermate. P21 jj and nj Gunn rats were re-tested in three weeks in the same condition. ABR with 100-microsecond pulse width click and DPOAEs at 8 kHz, 16 kHz and 22 kHz were measured before and after 1 mg/kg sulfadimethoxine injection. RESULTS: The thresholds of ABR were elevated in P19 and P21 group within the first day after injection and became normalized at several days after injection. Delay of wave II, III, IV and V were also observed. DPOAE showed no significant change after injection in all groups, meaning that the cochlea was not damaged. CONCLUSION: This study shows that bilirubin ototoxicity is related with pathologic changes at or higher than the brainstem level with intact cochlear function. Changes in ABR findings were only observed in P19 and P21 groups because they had higher bilirubin level in blood and their central auditory pathway is more immature than that found in the P42 group. In this study, we also found the possibility of spontaneous recovery from hyperbilirubinemia-related auditory toxicity.
Animals ; Auditory Pathways ; Basal Ganglia ; Bilirubin* ; Brain ; Brain Stem ; Cochlea ; Evoked Potentials, Auditory, Brain Stem ; Hearing Loss, Sensorineural ; Hyperbilirubinemia ; Hyperbilirubinemia, Neonatal ; Models, Animal ; Otoacoustic Emissions, Spontaneous ; Rats ; Rats, Gunn* ; Sulfadimethoxine