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Teratogenicity Evaluation of 2-Bromopropane Using Rat Whole Embryo Culture  

Kim Jong-Choon (College of Veterinary Medicine, Chonnam National University)
Shin Dong-Ho (College of Veterinary Medicine, Chonnam National University)
Kim Sung-Ho (College of Veterinary Medicine, Chonnam National University)
Yang Young-Soo (College of Veterinary Medicine, Chonnam National University)
Oh Ki-Seok (College of Veterinary Medicine, Chonnam National University)
Jiang Cheng-Zhe (Center for Safety Evaluation and Research of Drugs, Institute of Laboratory, Animal Science. CAMS, Peking Union Medical College)
Chung Moon-Koo (Korea Institute of Toxicology, KRICT)
Publication Information
Toxicological Research / v.22, no.2, 2006 , pp. 127-133 More about this Journal
Abstract
Recently, we have reported that the environmental pollutant 2-bromopropane (2-BP) induces a significant embryo-fetal developmental toxicity in rats. However, the cause of developmental toxicity and the relationship between maternal and developmental toxicities could not be elucidated because the developmental toxicity of 2-BP was observed only in the presence of maternal toxicity The in vitro teratogenicity study using whole embryo culture was carried out to understand the teratogenic properties and the possible mechanism of teratogenicity induced by 2-BP in rats. Rat embryos aged 9.5 days were cultured in vitro for 48 hrs at medium concentrations of 0, 1, 3, or 10 mg/ml of 2-BP. Embryos were evaluated for growth, differentiation, and morphological alterations at the end of the culture period. At 10 mg/ml, 2-BP caused a delay in the growth and differentiation of embryos and an increase in the incidence of morphological alterations, including altered yolk sac circulation, abnormal axial rotation, craniofacial hypoplasia, open neuropore, absent optic vesicle and kinked somites. At 3 mg/ml, only a delay in the growth and differentiation of embryos was observed. There were no adverse effects on embryonic growth and development at the concentration of 1 mg/ml. The results showed that the exposure of 2-BP to rat embryos results in a developmental delay and morphological alterations at dose levels of 3 mg/ml culture media or higher and that 2-BP can induce a direct developmental toxicity in rat embryos.
Keywords
2-Bromopropane; Embryotoxicity; Teratogenicity; In vitro; Rats;
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1 Bradford, M.M. (1976): A rapid sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anat. Biochem., 72, 248-254   DOI   ScienceOn
2 Chung, M.K., Kim, J.C. and Han SS. (2005): Embryotoxic effects of CKD-602, a new camptothecin anticancer agent, in rats. Reprod. Toxicol., 20, 165-173   DOI   ScienceOn
3 Ishikawa, H., Tian, Y. and Yamauchi, T. (2001): Induction of micronuclei formation in preimplantation mouse embryos after maternal treatment with 2-bromopropane. Reprod. Toxicol., 15, 81-85   DOI   ScienceOn
4 Kang, K.S., Li, G.X., Che, J.H. and Lee, Y.S. (2002): Impairment of male rat reproductive function in F1 offspring from dams exposed to 2-bromopropane during gestation and lactation. Reprod. Toxicol., 16, 151-159   DOI   ScienceOn
5 Kawai, T., Okada, Y., Odachi, T., Horigichi, S., Zhang, Z., Moon, C. and Ikeda, M. (1997): Diffusive sampling and biological monitoring of 2-bromopropane. Arch. Environ. Contam. Toxicol., 33, 23-28   DOI
6 Kim, J.C., Shin, D.H., Kim, S.H., Ahn, T.H., Kang, S.S., Jang, B.S., Kim, C.Y. and Chung, M.K. (2003): Developmental toxicity evaluation of the new fluoroquinolone antibacterial DW-116 in rats. Teratog. Carcinog. Mutagen., 23, 123- 136   DOI   ScienceOn
7 Kruskal, W.H. and Wallis, W.A. (1952): Use of ranks in one criterion variance analysis. J. Am. Statist. Assoc., 47, 614- 617
8 NRC (National Research Council). (1996): Guide for the Care and Use of Laboratory Animals. National Research Council, National Academy, Washington, USA
9 van Maele-Fabry, G., Delhaise, F. and Picard, J.J. (1990): Morphogenesis and quantification of the development of post-implantation mouse embryos. In vitro, 4, 149-156   DOI   ScienceOn
10 Kim, J.C., Kim, S.H., Shin, D.H., Ahn, T.H., Kim, H.C., Kim, Y.B., Jiang, C.Z., Han, J. and Chung, M.K. (2004): Effects of prenatal exposure to the environmental pollutant 2-bromopropane on embryo-fetal development in rats. Toxicology, 196, 77-86   DOI   ScienceOn
11 김종춘, 신진영, 신동호, 강성철, 정나영, 백성수, 정문구 (2004): 발생독성 검색을 위한 마우스 전배자배양법의 확립. 한국실험동물학회지, 20, 49-54
12 Zhao, L.X., Kim, E.K., Lim, H.T., Moon, Y.S., Kim, N.H., Kim, T.H., Choi, H., Chae, W., Jeong, T.C. and Lee, E.S. (2002): Synthesis, characterization and in vitro identification of N7-guanine adduct of 2-bromopropane. Arch. Pharm. Res., 25, 39-44   DOI   ScienceOn
13 HSDB. Hazardous Substances Data Bank, Bethesda (MD). (2001): National Institutes of Health. Available from URL: http://toxnet.nlm.nih.gov
14 Kim, J.C., Shin, H.C., Cha, S.W., Koh, W.S., Chung, M.K. and Han, S.S. (2001): Evaluation of developmental toxicity in rats exposed to the environmental estrogen bisphenol A during pregnancy. Life Sci., 69, 2611-2625   DOI   ScienceOn
15 Wise, L.D., Beck, S.L., Beltrame, D., Beyer, B.K., Chahoud, I., Clark, R.L., Clark, R., Druga, A.M., Feuston, M.H., Guittin, P., Henwood, S.M., Kimmel, C.A., Lindstrom, P., Palmer, A.K., Petrere, J.A., Solomon, H.M., Yasuda, M. and York, R.G. (1997): Terminology of developmental abnormalities in common laboratory mammals (Version 1). Teratology, 55, 249-292   DOI   ScienceOn
16 New, D.A.T. (1978): Whole-embryo culture and the study of mammalian embryos during organogenesis. Biol. Rev., 53, 81-122   DOI   ScienceOn
17 Wu, X., Faqi, A.S., Yang, J., Pang, B.P., Ding, X., Jiang, X. and Chahoud, I. (2002): 2-Bromopropane induces DNA damage, impairs functional antioxidant cellular defenses, and enhances the lipid peroxidation process in primary cultures of rat Leydig cells. Reprod. Toxicol., 16, 379-384   DOI   ScienceOn
18 Yu, X., Kamijima, M., Ichihara, G., Li, W., Kitoh, J., Xie, Z., Shibata, E., Hisanaga, N. and Takeuchi, Y. (1999): 2-Bromopropane causes ovarian dysfunction by damaging premordial follicles and their oocytes in female rats. Toxicol. Appl. Pharmacol., 159, 185-193   DOI   ScienceOn
19 Kim, J.C., Yun, H.I., Shin, H.C., Han, S.S. and Chung, M.K. (2000): Embryo lethality and teratogenicity of a new fluoroquinolone antibacterial DW-116 in rats. Arch. Toxicol., 74, 120-124   DOI
20 Kavlock, R.J., Chernoff, N. and Rogers, E.H. (1985): The effect of acute maternal toxicity on fetal development in the mouse. Teratog. Carcinog. Mutagen., 5, 3-13   DOI   ScienceOn
21 Dunnett, C.W. (1964): New tables for multiple comparisons with a control. Biometrics, 20, 482-491   DOI   ScienceOn
22 Nelson, B.K., Brightwell, W.S., MacKenzie-Taylor, D.R., Khan, A., Burg, J.R., Weigel, W.W. and Goad, P.T. (1988): Teratogenicity of n-propanol and isopropanol administered at high inhalation concentrations to rats. Food Chem. Toxicol., 26, 247-254   DOI   ScienceOn
23 Khera, K.S. (1987): Maternal toxicity in human and animals: effects on fetal development and criteria for detection. Teratog. Carcinog. Mutagen., 7, 287-295   DOI   ScienceOn
24 Omura, M., Romero, Y., Zhao, M. and Inoue, N. (1999): Histopathological evidence that spermatogonia are the target cells of 2-bromopropane. Toxicol. Lett., 104, 19-26   DOI   ScienceOn
25 Yamaguchi, C., Fujita, S., Obara, T. and Ueda, T. (1983): Effects of room temperature on reproduction, body weight and organ weights, food and water intakes, and hematology in mice. Exp. Anim., 32, 1-11   DOI
26 Park, J.S., Kim, Y.H., Park, D.W., Choi, K.S., Park, S.H. and Moon, Y.H. (1997): An outbreak of hematopoietic and reproductive disorders due to solvents containing 2-bromopropane in an electronic factory, South Korea: Epidemiological survey. J. Occup. Health, 39, 38-143
27 Chernoff, N., Rogers, J.M. and Kavlock, R.J. (1989): An overview of maternal toxicity and prenatal development: considerations for developmental toxicity hazard assessments. Toxicology, 59, 111-125   DOI   ScienceOn
28 Mirkin, B.L. (1973): Maternal and fetal distribution of drugs in pregnancy. Clin. Pharmacol. Ther., 14, 643-647   DOI
29 Chahoud, I., Ligensa, A., Dietzel, L. and Faqi, A.S. (1999): Correlation between maternal toxicity and embryo/fetal effects. Reprod. Toxicol., 13, 375-381   DOI   ScienceOn