| Co-Investigator(Kenkyū-buntansha) |
MIYOSHI Takanori University of Tokushima, Institute of Health Biosciences, Assistant Professor, 大学院・ヘルスバイオサイエンス研究部, 助手 (20346612)
UCHIHARA Hiroshi Horiba Ltd., Kyoto, 分析センター, 研究職
ISHIKAWA Sumiyo Horiba Ltd., Kyoto, 分析センター, 研究職
門田 康正 徳島大学, 医学部, 教授 (60028628)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
It is known that chromium is an inhaled carcinogen and an important risk factor in the development of lung carcinoma.
METHODS 1 and 2 : The authors used a microscopic X-ray fuorescence analyzer with transmitted X-ray mapping imaging (Horiba, Kyoto, Japan) to measure the accumulation of chromium in 10 resected lung tissue specimens and 90 biopsy specimens from chromate workers. RESULTS 1 and 2 : The maximum chromium accumulation (mean ± standard deviation) in 10 resected lung tissue specimens was 197 ± 238 counts per second (cps)/mili ampere (mA) (range, 4-649 cps/mA). Chromium accumulation was scattered in six tissue specimens and diffuse in one specimen. Chromium accumulation in the proximal bronchi was less than in the bronchioles or subpleural regions of the lung. Chromium accumulation was detectable in 63 (70%) of 90 biopsy specimens, and the mean accumulation was 6.5 ± 9.2 cps/mA (range, 0-46.5 cps/mA). Chromium detected in bronchial tissue specimens was deposited in the bronchial
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stroma but not in the epithelium. The maximum chromium accumulations in dysplastic (n=3), squamous metaplastic (n=10), and normal bronchial epithelia (n=9) in chromate workers and in normal bronchial epithelia (n=3) in non-chromate workers were 20.2 ± 5.4, 18.3 ± 12.2, 13.2 ± 13.4, and 3.0 ± 1.8 cps/mA, respectively. The amount of chromium accumulation significantly increased according to the progression of malignant change of the bronchial epithelium (P=0.003).
METHODS 3 : We examined the replication error (RER) and loss of heterozygosity (LOH) in DNA of dysplastic (n=3), squamous metaplastic (n=10) tissues, using six microsatellite markers containing CA repeats : D3S647 (3p23), D3S966 (3p21.3), D3S1289 (3p21.1), D5S346 (5q21-q22), D9S161 (9p21), and TP53 (17p13.1). The RER phenotype was defined as the presence of microsatellite instability (MSI) at two or more loci. RESULTS 3 : Five (78.9%) of 9 premalignant lesions exhibited RER.
CONCLUSIONS : Considering genetic aberrations and chromium accumulation in these premalignant lesions is useful for elucidating the process of carcinogenesis in chromium-induced lung carcinoma. Less
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