Microscopical analysis of the chromium content in the bronchial and lung tissues of chromate workers and genomic changes of the premalignant lesions.

众所周知，铬是一种吸入性致癌物，是肺癌发生的重要危险因素。方法1和2：作者使用带有透射x射线测绘成像的显微x射线荧光分析仪（堀场，京都，日本）测量了铬酸盐工人的10个切除肺组织标本和90个活检标本中铬的积累。结果1和2:10个肺组织标本的最大铬积累（平均值±标准差）为197±238计数/秒(cps)/毫安（mA）（范围4 ~ 649 cps/mA）。铬在6个组织标本中呈分散累积，在1个组织标本中呈弥漫性累积。近端支气管的铬积累少于肺细支气管或胸膜下区域。90例活检标本中63例（70%）检测到铬积累，平均积累为6.5±9.2 cps/mA（范围0-46.5 cps/mA）。支气管组织标本中检出的铬主要沉积在支气管间质中，上皮中未见铬沉积。铬酸盐工人发育不良（n=3）、鳞状化生（n=10）、正常支气管上皮（n=9）和非铬酸盐工人正常支气管上皮（n=3）的最大铬累积量分别为20.2±5.4、18.3±12.2、13.2±13.4和3.0±1.8 cps/mA。根据支气管上皮恶性病变的进展，铬的蓄积量显著增加（P=0.003）。方法3：利用含有CA重复序列的6个微卫星标记：D3S647 （3p23）、D3S966 （3p21.3）、D3S1289 （3p21.1）、D5S346 （5q21-q22）、D9S161 （9p21）和TP53 (17p13.1)，检测发育不良（n=3）、鳞状化生（n=10）组织DNA的复制误差（RER）和杂合性缺失（LOH）。RER表型被定义为在两个或多个位点存在微卫星不稳定性（MSI）。结果3:9例癌前病变中有5例（78.9%）表现为RER。结论：考虑这些癌前病变的遗传畸变和铬积累有助于阐明铬诱导肺癌的癌变过程。少

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 … More 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