Effects of Toluene, Xylene and Trichloroethylene on the Regulation of GnRH, GnRH Receptor and Pit-1 Gene Expression in Male Rat Hypothalamus and Pituitary / 대한산업의학회지

The workplace exposure of chemicals has steadily increased, therefore the concern for subsequent effect on reproductive outcome has been an important issue in occupational medicine. In previous studies, higher rates of spontaneous abortion, reduced fertility and menstrual disorder among women, and an impairment of sperm quantity and quality among men have been associated with a wide variety of chemical agents. This study was conducted to evaluate the effects of toluene, xylene and trichloroethylene (TCE) injection on the mRNA levels of GnRH, GnRH receptor and Pit-1 genes in male rats hypothalamus and pituitary and the effects on the plasma levels of FSH, LH, prolactin and testosterone. Sprague-Dawley male rats were divided into five groups of five each according to concentration of toluene, xylene and TCE. The rats were injected subcutaneously to 0, 50, 100, 200, 400 mg/kg body weight/day of toluene, xylene and TCE, respectively for 6 days. Rat brains were excised and hypothalamus and pituitary were separated. Reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay (RPA) were used to evaluate the GnRH, GnRH receptor and Pit-1 mRNA levels. Plasma concentrations of FSH, LH, prolactin and testosterone were assayed by radioimulunoassay (RIA). The results were as follows; 1. GnRH, GnRH receptor and Pit-1 mRNA levels in toluene and xylene injected groups, and GnRH receptor mRNA levels in TCE injected group were lowered dose-dependently. Especially, GnRH receptor and Pit-1 mRNA levels in 200 mg/kg of toluene injected group, and GnRH, GnRH receptor and Pit-1 mRNA levels in 400 mg/kg of toluene injected group were significantly lowed than control group (p<0.05). GnRH receptor and Pit-1 mRNA levels in 400 mg/kg of xylene injected group, and GnRH receptor mRNA levels in 400 mg/kg of TCE injected group were significantly lower than control group (p<0.05). 2. The plasma levels of prolactin and testosterone in 400 mg/kg of toluene injected group, and LH in 100, 200 and 400 mg/kg of xylene injected group, and testosterone in 400 mg/kg of TCE injected group were significantly lower than control group (p<0.05). In conclusion, we speculated that toluene and xylene affected reproductive system secondarily through hypothalamus-pituitary axis, and TCE affected directly through steroidogenesis. And we recomended that further study for assessment of the reproductive toxiclty of mixed organic solvent exposures should be conducted.

Selenium Effect on the Frequency of SCEs Induced by Heavy Metals in Human Lymphocytes / 예방의학회지

The protective effect of sodium selenite (Na2SeO3) against the cytogenetic toxicity of heavy metals was investigated on human whole-blood cultures in relation to induction of sister chromatid exchange(SCE) in secondary metaphase chromosome. Methlmercury chloride (CH3HgCl), cadmium chloride (CdCl2), Potassium dichromate (K2Cr2O7), and sodium selenite caused to the typically dose-dependent increase in sister chromatid exchanges (SCEs) by the concentrations ranging from 0.3 micro M to 10 micro M. However, the inductions of sister chromatid exchanges by methymercury chloride or cadmium chloride were inhibited by the simultaneous addition of sodium selenite 1.2 micro M. The frequencies of SCE were decreased to the level of control in the molar ratios as 2 : 1, 1 : 1, 1 : 2, and 1 : 4 of selenium selenite vs. methylmercury chloride, and as 1 : 1 and 1 : 2 of selenium selenite vs. cadmium chloride, while the frequencies of SCE induced by potassium dichromate were not changed by the addition of sodium selenite in culture condition. Mitotic indices were decreased in the higher concentrations of chemicals and not significantly changed by the simultaneous addition of sodium selenite to the culture condition containing each chemicals.