メラノサイトの増殖・分化に対する放射線の影響に関する研究

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研究内容

マウスのメラノサイトの増殖・分化に対する放射線の影響の機構を明らかにすることを目標に、[1] 無血清初代培養系を用いてガンマ線や紫外線のメラノサイトの増殖・分化に対する影響の機構について明らかにし、また[2] マウスの毛色に関するコンジェニックマウスを作り、ガンマ線によるメラノサイトの増殖・分化に対する影響の機構をin vivoで明らかにした。

ガンマ線や紫外線による培養メラノサイトの増殖・分化に対する影響の機構の解析

マウスの新生児の背側皮膚より表皮細胞浮遊液を得て、これを無血清培養液で、メラノブラスト、メラノサイト及びケラチノサイトを初代純粋培養することに世界で初めて成功した。純粋培養およびそれらの混合培養を用いてガンマ線によるメラノサイトの増殖・分化に与える影響を調べ、ガンマ線で障害を受けるのはケラチノサイトで、その影響でメラノサイトの増殖・分化が抑制されることを明らかにした。マウスの皮膚に紫外線を照射して約二ヶ月後に形成される色素斑のケラチノサイトは、対照の皮膚由来のケラチノサイトに比べ、無血清初代培養系でメラノサイトの増殖・分化を有意に促進することを明らかにした。これは紫外線で変化するのはケラチノサイトの方で、ケラチノサイトにおけるメラノサイト増殖・分化促進因子産生が高められた可能性を示す。抗体を用いた研究からその因子の本体は、エンドセリン、スティール因子、顆粒球マクロファージコロニー形成促進因子であることを明らかにした。

毛色のコンジェニックマウスのメラノサイトの増殖・分化に対する影響の機構の解析

C57BL/10JHir系統マウスに毛色の突然変異遺伝子を導入し毛色に関するコンジェニックマウスを多数 (9系統)、世界で初めて作り、これを用いて、ガンマ線のメラノサイトの増殖・分化に対する影響を調べた。その結果、胎児期に照射を受けた子の腹部や尾端に白斑が高頻度で現れ、この白斑部分にはメラノブラスト・メラノサイトが欠損していることを明らかにした。これは、ガンマ線によりメラノブラストの増殖が抑制されたためと考えられる。さらにメラノブラストの欠損は見られなくても毛球には樹枝状突起を形成していない丸いメラノサイトが多数出現することを明らかにし、それらの効果はマウスの発生の時期に特異的に効くことを明らかにした。また、炭素線でも線量依存的に腹部・尾端白斑を引き起こすことも明らかにしてきた。

研究内容(原著論文目録)

  1. T. Yamaguchi, T. Hirobe, Y. Kinjo and K. Manaka. The effect of chalone on the cell cycle in the epidermis during during wound healing. Exp. Cell Res. 89:247-254(1974).
  2. T. Yamaguchi and T. Hirobe. The effect of chalone on the cell kinetics in the epidermis during wound healing or organ culture. "Biochemistry of Cutaneous Epidermal Differentiation" M. Seiji and I. A. Bernstein eds., Univ. Tokyo Press, Tokyo, pp181-201(1977).
  3. T. Hirobe and T. Takeuchi. Induction of melanogenesis in the epidermal melanoblasts of newborn mouse skin by MSH. J. Embryol. Exp. Morph. 37:79-90(1977).
  4. T. Hirobe and T. Takeuchi. Induction of melanogenesis in vitro in the epidermal melanoblasts of newborn mouse skin by MSH. In vitro 13:311-315(1977).
  5. T. Hirobe and T. Takeuchi. Changes of organelles associated with the differentiation of epidermal melanocytes in the mouse. J. Embryol. Exp. Morph. 43:107-121(1978).
  6. 広部知久:ほ乳類のメラノサイトに対するMSHの効果について。動物学雑誌 87:177-185(1978).
  7. T. Hirobe. Stimulation of dendritogenesis in the epidermal melanocytes of newborn mice by melanocyte-stimulating hormone. J. Cell Sci. 33:371-383(1978).
  8. T. Hirobe. Genes involved in regulating the melanocyte and melanoblast-melanocyte populations in the epidermis of newborn mouse skin. J. Exp. Zool. 223:257-264(1982).
  9. T. Hirobe. Origin of melanosome structures and cytochemical localizations of tyrosinase activity in differentiating epidermal melanocytes of newborn mouse skin. J. Exp. Zool 224:355-363(1982).
  10. T. Hirobe. Effects of actinomycin D and cycloheximide on the differentiation of epidermal melanocytes of newborn mice. Exp. Anim. 32:21-27(1983).
  11. T. Hirobe. Proliferation of epidermal melanocytes during the healing of skin wounds in newborn mice. J. Exp. Zool. 227:423-431(1983).
  12. T. Hirobe. Histochemical survey of the distribution of the epidermal melanoblasts and melanocytes in the mouse during fetal and postnatal periods. Anat. Rec. 208:589-594(1984).
  13. T. Hirobe. Effects of genic substitution at the brown locus on the differentiation of epidermal melanocytes in newborn mouse skin. Anat. Rec. 209:425-432(1984).
  14. Y. Wakamatsu, A. Oikawa, M. Obika, T. Hirobe and K. Ozato. Fish hereditary melanoma cell lines of different degrees of cell differentiation. Dev. Growth Diff. 25:503-513(1984).
  15. T. Hirobe. Genetic factors involved in regulating the melanocyte and melanoblast-melanocyte populations in the mouse epidermis. "Pigment Cell 1985. Biological, Molecular and Clinical Aspects of Pigmentation" J. Bagnara, S. N. Klaus, E. Paul and M. Schartl eds., Univ. Tokyo Press, Tokyo, pp359-367(1985).
  16. Y. Wakamatsu, A. Oikawa, M. Obika, T. Hirobe and K. Ozato. Establishment and characterization of four cell lines derived from hereditary melanomas in Xiphophorus fish hybrids. "Pigment Cell 1985. Biological, Molecular and Clinical Aspects of Pigmentation" J. Bagnara, S. N. Klaus, E. Paul and M. Schartl eds., Univ. Tokyo Press, Tokyo, pp449-456(1985).
  17. H. B. Tamate, T. Hirobe and T. Takeuchi. Effects of the lethal yellow (Ay) and recessive yellow (e) genes on the population of epidermal melanocytes in newborn mice. J. Exp. Zool. 238:235-240(1986).
  18. H. B. Tamate, T. Hirobe and K. Ishikawa Tyrosinase abundance and melanization in skin of neonatal mice with various coat-color genotypes. Str. Func. Melanin 3:44-52(1986).
  19. T. Hirobe. Genetic control of the population size of the melanocyte in the mouse epidermis. Jpn. J. Genet. 62:149-158(1987).
  20. G. Szabo, T. Hirobe, E. A. Flynn and R. I. Garcia. The biology of the melanocyte. "Advances in Pigment Cell Research" J. Bagnara ed., Alan R. Liss, New York, pp463-474(1988).
  21. T. Hirobe. Developmental changes of the proliferative response of mouse epidermal melanocytes to skin wounding. Development 102:567-574(1988).
  22. T. Hirobe, E. Flynn, G. Szabo, M. vrabel and R. I. Garcia. Growth characteristics of human epidermal melanocytes in pure culture with special reference to genetic differences. J. Cell. Physiol. 135:262-268(1988).
  23. T. Hirobe. Genetic factors controlling the proliferative activity of mouse epidermal melanocytes during the healing of skin wounds. Genetics 120:551-558(1988).
  24. H. B. Tamate, T. Hirobe, K. Wakamatsu, S. Ito, S. Shinic substitution at the agouti, brown, albino, dilute, and pink-eyed dilution loci. J. Exp. Zool. 250:304-311(1989).
  25. T. Hirobe and X. Zhou. Effects of gamma-radiation on the differentiation of mouse melanocytes in the hair follicles. Mutation Res. 234:91-96(1990).
  26. T. Hirobe. Selective growth and serial passage of mouse melanocytes from neonatal epidermis in a medium supplemented with bovine pituitary extract. J. Exp. Zool. 257:184-194(1991).
  27. T. Hirobe. Developmental interactions in the pigmentary system of the tip of the mouse tail: Effects of coat-color genes on the expression of a tail-spotting gene. J Exp. Zool. 258:353-358(1991).
  28. Y. Matsuda, T. Hirobe and v. M. Chapman. Genetic basis of X-Y chromosome dissociation and male sterility in interspecific hybrids. Proc. Natl. Acad. Sci. USA. 88:4850-4854(1991).
  29. T. Hirobe. Basic fibroblast growth factor stimulates the sustained proliferation of mouse epidermal melanoblasts in serum-free medium in the presence of dibutyryl cyclic AMP and keratinocytes. Development 114:435-445(1992).
  30. T. Hirobe. Control of melanocyte proliferation and differentiation in the mouse epidermis. Pigment Cell Res. 5:1-11(1992).
  31. T. Hirobe. Melanocyte stimulating hormone induces the differentiation of mouse epidermal melanocytes in serum-free culture. J. Cell. Physiol. 152:337-345(1992).
  32. T. Hirobe. Keratinocytes are involved in regulating the developmental changes in the proliferative activity of mouse epidermal melanoblasts in serum-free culture. Dev. Biol. 161:59-69(1994).
  33. T. Hirobe. Effects of activators (SC-9 and OAG) and inhibitors (staurosporine and H-7) of protein kinase C on the proliferation of mouse epidermal melanoblasts in serum-free culture. J. Cell Sci. 107:1679-1686(1994).
  34. T. Hirobe. Effects of γ-irradiation on the yield of mid-ventral white spots in mice in different genetic backgrounds and at different times during development. Mutation Res. 322:213-220(1994).
  35. T. Hirobe. Structure and function of melanocytes: Microscopic morphology and cell biology of mouse melanocytes in the epidermis and hair follicle. Histol. Histopathol. 10:223-237(1995).
  36. H. Ozeki, S. Ito, K. Wakamatsu and T. Hirobe. Chemical characterization of hair melanins in various coat-color mutants of mice. J. Invest. Dermatol. 105:361-366(1995).
  37. T. Hirobe. Hydrocortisone is involved in regulating the proliferation and differentiation of mouse epidermal melanoblasts in serum-free culture in the presence of keratiocytes. Eur. J. Cell Biol. 71:387-394(1996).
  38. S. Fushiki, Y. Hyodo-Taguchi, C. Kinoshita, Y. Ishikawa and T. Hirobe. Short- and long-term effects of low-dose prenatal X-irradiation in mouse cerebral cortex, with special reference to neuronal migration. Acta Neuropathol. 93:443-449(1997).
  39. Y. Hyodo-Taguchi, S. Fushiki, C. Kinoshita, Y. Ishikawa and T. Hirobe. Effects of continuous low-dose prenatal irradiation on neuronal migration in mouse cerebral cortex. J. Rad. Res. 38:87-94(1997).
  40. T. Hirobe, K. Wakamatsu and S. Ito. Effects of genic substitution at the agouti, brown, albino, dilute, and pink-eyed dilution loci on the proliferation and differentiation of mouse epidermal melanocytes in serum-free culture. Eur. J. Cell Biol. 75:184-191(1998).
  41. Y. Hyodo-Taguchi, S. Fushiki, C. Kinoshita, Y. Ishikawa and T. Hirobe. Effects of low-dose X-irradiation on the development of the mouse cerebellar cortex. J. Rad. Res. 39:11-19(1998).
  42. R. Furuya, S. Akiu, M. Naganuma, M. Fukuda and T. Hirobe. The proliferation and differentiation of neonatal epidermal melanocytes in hairless mice of (HR-1 x HR/De) F1 in serum-free culture. J. Dermatol. 25:211-221(1998).
  43. T. Hirobe and H. Abe. Genetic and epigenetic control of the proliferation and differentiation of mouse epidermal melanocytes in culture. Pigment Cell Res. 12:147-163(1999).
  44. T. Hirobe and H. Abe. ACTH4-12 is the minimal message sequence required to induce the differentiation of mouse epidermal melanocytes in serum-free primary culture. J. Exp. Zool. 286:632-640(2000).
  45. T. Kunisada, H. Yamazaki, T. Hirobe, S. Kamei, M. Omoteno, H. Tagaya, H. Hemmi, U. Koshimizu, T. Nakamura and S. Hayashi. Keratinocyte expression of transgenic hepatocyte growth factor affects melanocyte development, leading to dermal melanocytosis. Mech. Dev. 94:67-78(2000).
  46. T. Hirobe. Endothelins are involved in regulating the proliferation and differentiation of mouse epidermal melanocytes in serum-free primary culture. J. Invest. Dermatol. Symp. Proc. 6:25-31(2001).
  47. T. Hirobe, Y. Kawa, M. Mizoguchi, S. Ito and K. Wakamatsu. Effects of genic substitution at the pink-eyed dilution locus on the proliferation and differentiation of mouse epidermal melanocytes in vivo and in vitro. J. Exp. Zool. 292:351-366(2002).
  48. T. Hirobe, K. Wakamatsu, S. Ito, H. Abe, Y. Kawa and M. Mizoguchi. Stimulation of the proliferation and differentiation of mouse pink-eyed dilution epidermal melanocytes by excess tyrosine in serum-free primary culture. J. Cell. Physiol. 191:162-172(2002).
  49. T. Hirobe. Role of leukemia inhibitory factor in the regulation of the proliferation and differentiation of neonatal mouse epidermal melanocytes in culture. J. Cell. Physiol. 192:315-326(2002).
  50. R. Furuya, S. Akiu, R. Ideta, M. Naganuma, M. Fukuda and T. Hirobe. Changes in the proliferative activity of epidermal melanocytes in serum-free primary culture during the development of UvB-induced pigmented spots in hairless mice. Pigment Cell Res. 15:348-356(2002).
  51. T. Hirobe, R. Furuya, S. Akiu, O. Ifuku and M. Fukuda. Keratinocytes control the proliferation and differentiation of cultured epidermal melanocytes from ultraviolet radiation B-induced pigmented spots in the dorsal skin of hairless mice. Pigment Cell Res. 15:391-399(2002).
  52. T. Hirobe, K. Wakamatsu and S. Ito. Changes in the proliferation and differentiation of neonatal mouse pink-eyed dilution melanocytes in the presence of excess tyrosine. Pigment Cell Res. 16:619-628(2003).
  53. T. Hirobe, M. Osawa and S-I. Nishikawa. Steel factor controls the proliferation and differentiation of neonatal mouse epidermal melanocytes in culture. Pigment Cell Res. 16:644-655(2003).
  54. T. Hirobe, M. Osawa and S-I. Nishikawa. Hepatocyte growth factor controls the proliferation of cultured epidermal melanoblasts and melanocytes from newborn mice. Pigment Cell Res. 17:51-61(2004).
  55. T. Hirobe, R. Furuya, E. Hara, I. Horii, M. Tsunenaga and O. Ifuku. Granulocyte-macrophage colony-stimulating factor controls the proliferation and differentiation of mouse epidermal melanocytes from pigmented spots induced by ultraviolet radiation B. Pigment Cell Res. 17:230-240(2004).
  56. T. Hirobe, R. Furuya, O. Ifuku, M. Osawa, and S-I. Nishikawa. Granulocyte-macrophage colony-stimulating factor is a keratinocyte-derived factor involved in regulating the proliferation and differentiation of neonatal mouse epidermal melanocytes in culture. Exp. Cell Res. 297:593-606 (2004).
  57. T. Hirobe, S. Takeuchi, E. Hotta, K. Wakamatsu and S. Ito. Pheomelanin production in the epidermis from newborn agouti mice is induced by the expression of the agouti gene in the dermis. Pigment Cell Research17:506-514(2004).
  58. T. Hirobe, K. Eguchi-Kasai and M. Murakami. Effects of carbon ion-radiations on the postnatal development of mice as well as on the yield of white spots in the mid-ventrum and the tail-tips. Radiat. Res. 162: 580-584(2004).
  59. T. Hirobe, S. Takeuchi and E. Hotta. The melanocortin receptor-1 gene but not the proopiomelanocortin gene is expressed in melanoblasts and contributes their differentiation in the mouse skin. Pigment Cell Res. 17:627-635(2004).
  60. T. Hirobe. Role of keratinocyte-derived factors involved in regulating the proliferation and differentiation of mammalian epidermal melanocytes. Pigment Cell Res. 18: 2-12(2005).
  61. T. Hirobe, K. Wakamatsu, S. Ito, Y. Kawa, Y. Soma and M. Mizoguchi. The slaty mutation affects eumelanin and pheomelanin synthesis in mouse melanocytes. Eur. J. Cell Biol. in press
  62. T. Hirobe, K. Wakamatsu and S. Ito. The contents of eumelanin and pheomelanin present in female hairs of recessive yellow mice are greater than in male hairs. Pigment Cell Res. in press
  63. 3.T. Hirobe and H. Abe. Slaty gene affects the formation of melanosomes and other organelles in the mouse epidermal melanocytes in culture. Pigment Cell Res. in press

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研究内容(日本語)

  1. 広部 知久 「正常メラノサイトの培養」 「現代皮膚科学大系 第4巻b 基礎皮膚科学実験法」 清寺 真編、中山書店、東京、pp204-207(1981).
  2. 若松 祐子・広部 知久 「下等脊椎動物色素細胞」「組織細胞化学の技術―無機物と色素」 小川 和朗・中根 一穂編、朝倉書店、東京、pp287-289(1994).
  3. 広部 知久 「メラノサイトの増殖・分化に働く外的要因―培養系での解析から」 「色素細胞―神経冠からの発生・分化の遺伝子機構から色素性疾患への対応を探る」松本 二郎・溝口 昌子編、慶応大学出版会、東京、pp39-49(2001).
  4. 広部 知久 「ほ乳類のメラノサイト」 細胞 23:513-518(1991).
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