• Archives of Pharmacal Research
• /
• 제28권10호
• /
• pp.1177-1182
• /
• 2005

The hepatotoxic effects of 1-bromopropane (1-BP) and its conjugation with glutathione were investigated in male ICR mice. A single dose (1000 mg/kg, po) of 1-BP in corn oil to mice significantly increased serum activities of alanine aminotransferase and aspartate aminotransferase. Glutathione (GSH) content was dose-dependently reduced in liver homogenates 12 h after 1-BP treatment. In addition, 1-BP treatment dose-dependently increased levels of S-pro-pyl GSH conjugate at 12 h after treatment, as measured by liquid chromatography-electro-spray ionization tandem mass spectrometry. The GSH conjugate was maximally increased in liver at 6 h after 1-BP treatment (1000 mg/kg), with a parallel depletion of hepatic GSH content. Finally, 1-BP induced the production of malondialdehyde in liver. The present results suggest that 1-BP might cause hepatotoxicity, including lipid peroxidation via the depletion of GSH, due to the formation of GSH conjugates in male ICR mice.

• Bulletin of the Korean Chemical Society
• /
• 제30권10호
• /
• pp.2318-2328
• /
• 2009

Massive deadenylation of adenine based-nucleosides induced by halogenated alkanes at the physiological condition have been observed. For the study of deadenylation effects by the different substituents and/or functionality in halogenated alkanes, diverse kinds of halogenated alkanes were incubated with adenine based-nucleosides (ddA, dA and adenosine) for 48 h at the physiological condition (pH 7.4, $37\;{^{\circ}C}$), which were analyzed by HPLC and further confirmed by LC-MS. Among the sixteen different halogenated alkanes, we observed massive deadenylation of nucleosides by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane. The order of deadenylation rate was highest in 2-bromo-2-methylpropane followed by 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane. In addition, time and dose response relationship of deadenylation in adenine based-nucleosides induced by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane at the physiological condition were investigated. In addition, deadenylation of calf thymus DNA induced by halogenated alkanes was also investigated. These results suggest that the toxic effect of certain halogenated alkanes might be from the depurination of nucleosides.

• Bulletin of the Korean Chemical Society
• /
• 제30권12호
• /
• pp.2949-2958
• /
• 2009

Massive deguanylation of guanine based-nucleosides induced by halogenated alkanes at the physiological condition have been observed. For the study of deguanylation effects by the different substituents and/or functionality in halogenated alkanes, diverse kinds of halogenated alkanes were incubated with guanine based-nucleosides (ddG, dG and guanosine) for 48 h at the physiological condition (pH 7.4, 37$^{\circ}C$), which were analyzed by HPLC and further confirmed by LC-MS. Among the sixteen different halogenated alkanes, we observed massive deguanylation of nucleosides by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane. The order of deguanylation rate was highest in 2-bromo-2-methylpropane followed by 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane. In addition, time and dose response relationship of deguanylation in guanine basednucleosides induced by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane at the physiological condition were investigated. Deguanylation of calf thymus DNA induced by halogenated alkanes was also investigated. These results suggest that the toxic effect of certain halogenated alkanes might be from the depurination of nucleosides.

• 한국발생생물학회지:발생과생식
• /
• 제5권2호
• /
• pp.107-114
• /
• 2001

환경호르몬(내분비계 장애물질)이 하등동물의 생식기 및 생식 기능 이상을 초래한다는 최근보고는 포유동물도 그 영향하에 있음을 암시한다. 따라서 2-bromopropane(2-BP)이 생쥐 차산자의 성별에 미치는 영향과 성 분화 과정 중에 발현되는 유전자를 조사하였다. 생쥐를 2-BP로 3주일 동안 주입한 암수를 4종류 조합으로 교배시 킨 후 태어난 새끼들의 성별을 이유시기에 결정하였다. 성관련 유전자들은 수태 후 10일에 어미 생쥐를 희생시켜 RT-PCR 방법으로 태자들에게서 발현되는 유전자를 탐지하였고, 동정된 범위의 핵산 서열을 기존의 보고된 서열과 비교 분석하였다. 이유시기까지 살아남은 한배 차산자 평균수는 암수를 모두 2-BP로 처리한 군에서만 약간 감소하였다. 차산자의 성비에서 암컷 어미가 2-BP로 처리된 군에서만 차산자 암컷이 수컷보다 많았으며, 그 이외의 군에서는 수컷이 암컷보다 많았다. 성 분화 시기에 발현되는 유전자들인 SRY 유전자는 416 염기, DAX1 유전자는 466 염기, SF1 유전자는 326 염기, AMH 유전자는 389 염기를 동정하였다. 이 유전자들은 흰쥐와는 89～90％의 상동성을, 그리고 사람과는 81～92％의 상동성을 보였다. 이 유전자들은 성이 결정되는 시기인 수태 10 일경에 모두 발현됨을 알 수 있었다. 따라서 2-BP는 생식능력에 어느 정도 영향을 미치는 것으로 사료된다. 포유동물의 성 분화에 미치는 내분비계 장애물질의 영향을 성관련 유전자들의 발현과 관련지어 연구할 수 있을 것으로 기대된다.

• 한국임상수의학회지
• /
• 제27권5호
• /
• pp.514-521
• /
• 2010

음양곽(Epimedicum Koreanum nakai)은 예부터 생식기 장애치료를 위해 사용되어 왔다. 본 연구에서는 2-브로모프로판(2-bromopropane; 2-BP)으로 유발된 생식기 장애에서 음양곽 물추출물의 생식기장애 치료효과를 평가하였다. 2-BP를 체중kg당 1,355 mg씩 28일간 피하로 투여하여 생식기 장애를 유발하였으며, 음양곽 추출물은 용량별(10, 100, 500 mg/kg)로 4주간 경구투여 하였다. 그 결과 일일정자생성(daily sperm production)은 대조군에 비하여 증가하였으나 용량의존적 감소를 나타내었으며, 정세관과 부고환관에서는 조직학적 유의한 변화를 나타내었다. 이러한 결과는 음양곽물추출이 2-BP로 유발된 생식기장애의 치료에 도움이 될 것으로 생각된다.

• 월간산업보건
• /
• 통권261호
• /
• pp.21-27
• /
• 2010

• 월간산업보건
• /
• 통권260호
• /
• pp.6-10
• /
• 2009

• 한국환경성돌연변이발암원학회:학술대회논문집
• /
• 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
• /
• pp.146-146
• /
• 2002

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 1998년도 국제심포지움 및 추계학술대회
• /
• pp.61-61
• /
• 1998

• Toxicological Research
• /
• 제19권3호
• /
• pp.227-234
• /
• 2003

2-Bromopropane (2-BP), a halogenated propane analogue, is a substitute for chlorofluorocarbones (CFCs) which have a great potential to destroy the ozone layer and to warm the earth's environment. The present study was undertaken to evaluate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GD) 6 through 17 in ICR mice. The test chemical was administered subcutaneously to pregnant mice at dose levels of 0, 313, 625 or 1,250 mg/kg/day. All dams were subjected to caesarean section on GD 18 and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1,250 mg/kg group, maternal toxicity included an increase in the incidence of abnormal clinical signs and a decrease in the maternal body weight, body weight gain, and corrected body weight. Developmental toxicity included a decrease in the fetal body weight, a reduction in the placental weight, an increase in the fetal skeletal variation and ossification delay. There were no adverse effects on either pregnant dams or embryo-fetal development in the 313 and 625 mg/kg groups. These results suggest that a 12-day subcutaneous dose of 2-BP is embryotoxic at a maternally toxic dose (i.e., 1,250 mg/kg/day) in ICR mice. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 625 mg/kg/day for dams and embryo-fetuses, respectively.