Environmental Health Perspectives 105, Supplement 5, September 1997

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Effects of Mineral Fibers on the Expression of Genes Whose Product May Play a Role in Fiber Pathogenesis

Tohru Tsuda, 1 Yasuo Morimoto, 1 Hiroshi Yamato, 1 Hiromi Nakamura, 1 Hajime Hori, 2 Nobuhiko Nagata, 3 Masamitsu Kido, 3 Toshiaki Higashi, 1 and Isamu Tanaka 1

1 Institute of Industrial Ecological Sciences, 2 School of Health Sciences, and 3 Department of Respiratory Disease, University of Occupational and Environmental Health, Kitakyushu, Japan

Abstract
To determine which factors are useful for the risk assessment of man-made fibers, we examined the gene expression of proinflammatory cytokines, growth factors, manganese superoxide dismutase (MnSOD), and inducible nitric oxide synthase (iNOS) in mineral fiber-exposed rats by means of reverse transcription-polymerase chain reaction (RT-PCR). Male Wistar rats received a single intratracheal instillation of either saline (control) or two types of fibers (2 mg of Union Internationale Centre le Cancer (UICC) chrysotile or alumina silicate refractory ceramic fiber [RCF]). Expression of interleukin-1 alpha (IL-1 alpha ), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF- alpha ), platelet-deriving growth factor-A, (PDGF-A), platelet-deriving growth factor-B (PDGF-B), transforming growth factor ß1 (TGF-ß1), basic fibroblast growth factor (bFGF), MnSOD, and iNOS mRNA from lung and lipopolysaccharide (LPS)-stimulated alveolar macrophages (AM) were assessed by RT-PCR. Among these factors, IL-1 alpha , TNF- alpha , IL-6, bFGF, and iNOS would be the possible parameters for the risk assessment of fibers. In a follow-up study, we investigated the time course (3 days, 1 week, 1 month, and 3 months) of expression of IL-1 alpha and TNF- alpha by LPS-stimulated AM exposed to mineral fibers in vivo . Male Wistar rats were instilled intratracheally with saline or fibers (2 mg of Union Internationale Contre le Cancer UICC crocidolite or potassium octatitanate whisker [TW]). The expression of IL-1 alpha mRNA by fibers was greatest in TW, crocidolite, chrysotile, and RCF-instilled rat AM, in that order. The increase of IL-1 alpha and TNF- alpha mRNA in AM peaked at 1 month and 3 days after exposure to crocidolite or TW, respectively. The expression of IL-1 alpha by fibers (crocidolite, chrysotile, TW, and RCF) may be a good indicator of the pathologic potential of fibers. -- Environ Health Perspect 105(Suppl 5):1173-1178 (1997)

Key words : man-made fiber, asbestos, risk assessment, RT-PCR, cytokine

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 23 April 1997.

Address correspondence to Dr. T. Tsuda, Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu, Japan 807. Telephone: 81 93 691 7466. Fax: 81 93 691 4284. E-mail: tsuda@med.uoeh-u.oc.jp

Abbreviations used: AM, alveolar macrophage(s); BAL, bronchoalveolar lavage; BALF, bronchoalveolar lavage fluid; bFGF, basic fibroblast growth factor; IL-6, interleukin-6; iNOS, inducible nitric oxide synthase; LPS, lipopolysaccharide; MMF, man-made fiber(s); MnSOD, manganese superoxide dismutase; NIH, National Institutes of Health; PDGF-A, platelet-deriving growth factor A; PDGF-B, platelet-deriving growth factor B; RCF, refractory fiber(s); RT-PCR, reverse transcription-polymerase chain reaction; TGF-ß1, transforming growth factor ß1; TNF- alpha , tumor necrosis factor alpha; TW, potassium octatitanate whisker; UICC, Union Internationale Contre le Cancer; UV, ultraviolet.

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Last Update: November 18, 1997