Kiyonobu Kimura

Chromate lung cancer with special reference to its cell type and relation to the manufacturing process

The manufacturing process of the chromate industry can be classified into five steps. The main hazardous pollutants of the first step are trivalent chromate compounds, and those of the second and third steps are hexavalent chromate compounds. Analysis of the detailed working history of chromate workers with bronchogenic carcinoma, yielded the following results: the work history of chromate lung cancer patients in the first step, which produced mainly trivalent chromate dust, was rather short. Patients with small cell carcinoma were engaged mainly in the second step (98.1% of the total working months), where they were heavily exposed to hexavalent chromate dusts. Patients with squamous cell carcinoma were engaged rather evenly in the second and fourth steps, and somewhat longer in the third step. Comparisons of the exposure periods revealed that the working history of small cell carcinoma patients was significantly shorter than that of squamous cell carcinoma patients. There were many more heavy smokers among the squamous cell carcinoma group as compared to the small cell carcinoma patients. Based on these results, it is concluded that the cell type of occupational lung cancer was mainly small cell carcinoma when the exposure to carcinogenic agents was heavy, and that the carcinogenicity of chromate was derived mainly from hexavalent chromate rather than trivalent compounds.

Silicosis, mixed dust pneumoconiosis, and lung cancer

A total of 764 autopsy cases with a pathological diagnosis of nonasbestos pneumoconiosis were investigated in a search for lung cancer: 146 patients bore 148 lung cancers (19.1%). The incidence of a lung cancer was associated positively with aging longer occupational exposures, and smoking habits. A reverse correlation was found between carcinogenesis and the severity of pneumoconiosis. A statistically significant increase in the incidence of certain types of lung cancer (squamous cell carcinoma + small cell carcinoma) was found in silicotic lungs with massive fibrosis as compared to lungs with mixed dust pneumoconiosis of comparable severity. Although there appears to be no dose-response relationship in general between silicosis and lung cancer, it is advisable to consider the possibility that a presumptive silica-induced carcinogenesis might be masked by the severe fibrosis of a silicotic type, which obliterates the lung tissue in a different way from asbestosis, which is associated with epithelial proliferation.

p53 and Bcl-2 expression in pneumoconiosis-related pre-cancerous lesions and lung cancers : Frequent and preferential p53 expression in pneumoconiotic bronchiolar dysplasias

To explore the mechanism by which lung cancers excessively arise from pneumoconiosis, we determined the altered expression of p53 and Bcl‐2 by immunohistochemistry (IHC) in lung cancers, dysplasias and non‐cancerous pulmonary epithelia in pneumoconiotics in comparison with those from non‐pneumoconiotic patients. We examined p53 expression in squamous cell carcinomas (SCCs) and dysplasias separately in the central and peripheral zones of bronchial trees, based on observations that SCCs from pneumoconiotic patients occurr more frequently in peripheral epithelia than those from non‐pneumoconiotic patients (55 of 72 SCCs with pneumoconiosis vs. 33 of 72 SCCs without pneumoconiosis). Forty‐one of 72 patients with pneumoconiosis‐related lung cancers had altered p53 expression, which was comparable to the positivity of p53 expression in lung cancers without pneumoconiosis. p53 expression was observed significantly more frequently in bronchiolar dysplasias with pneumoconiosis than in those from non‐pneumoconiotic patients (13 of 23 vs. 4 of 22), while p53 expression was found in bronchial dysplasias with pneumoconiosis as frequently as those without pneumoconiosis. Moreover, in patients with pneumoconiosis, bronchiolar dysplasias exhibited p53 expression more frequently than bronchial dysplasias (13 of 23 vs. 4 of 19). When comparison was restricted to bronchiolar dysplasias from patients without lung cancer, p53 expression had a strikingly higher frequency in the dysplasias with pneumoconiosis than in those from non‐pneumoconiotic patients (8 of 15 vs. 0 of 14). Bcl‐2 occasionally was expressed in squamous metaplasias and basal cell hyperplasias, in contrast to p53, for which immunostaining was negative in these lesions. Altogether, our results show that pre‐cancerous and/or cancerous targets in pneumoconiosis may be distributed over a more peripheral zone than those in patients without pneumoconiosis. Int. J. Cancer 75:504–511, 1998.© 1998 Wiley‐Liss, Inc.

Mannose-binding lectin gene polymorphisms and the development of coal workers' pneumoconiosis in Japan

BACKGROUND Infection, immunity and genetic factors play roles in the development of coal workers pneumoconiosis (CWP) and progressive massive fibrosis (PMF). We investigate whether the genetic polymorphisms of mannose-binding lectin (MBL), one of the key molecules of innate immunity, is associated with the susceptibility to CWP. METHOD MBL2 polymorphisms (codon54, promoter -221, and -550) were assessed for 197 patients with CWP (119 with nodular CWP and 78 with PMF) and 153 unexposed regional controls. Serum MBL concentrations were measured in 119 CWP patients. RESULTS Three polymorphisms were in linkage disequilibrium for all study populations. The MBL2 genotype and haplotypes were associated with lower serum MBL levels. The frequency of such MBL2 genotype and haplotypes were significantly higher in patients with CWP compared to controls, whereas these distributions were not different between patients with nodular CWP and those with PMF. CONCLUSION MBL2 polymorphisms and haplotypes may be one of the genetic determinants for the susceptibility of CWP.

Multiple Bronchogenic Carcinoma in Chromate Workers

クロムエ場従業員よりの3例の多発性肺癌-両側性-を経験した.内, 2例は両肺に生じた扁平上皮癌例であり, 1例は左肺に小細胞癌, 右肺に扁平上皮癌の同時発生例であった.扁平上皮癌両側発生例の内1例は手術を行った.1例は生前に診断を得たが病期が進行していたため死亡し、最後の例と共に剖検により子細に検索し得た.昭和56年春までにクロム工場従事者303名中, 21例の肺癌を見出し, この内, 剖検, 手術の可能な例8例であった.肺癌発生率の高頻度, また症例のような多発性肺癌を生ずることよりクロム塩類の強力な発癌性が示唆された.

A study on lung cancer among chromate workers Relationship between cell type and chromium compounds

クロム肺癌に発癌の関与する物質を検討するため, クロム酸塩製造工程別の従事期間を肺癌例と非癌例で検討した.肺癌例は6価クロムを取り扱う従事者に多かった.特に, 小細胞癌例では全従事期間のほとんど全てを水溶性の6価クロムを取り扱う工程に従事していた.クロム肺癌の発癌物質として, 水溶性の6価クロムが関与している可能性が示された.

A Case of Chromate Worker with Peripheral Type Adenocarcinoma

クロームエ場勤務歴32年間の職歴を有する肺癌症例を報告した. 本症例は, 切除肺組織中クローム含量が26μg/gwetweithtと高値を示し, クロームとの因果関係が強く示唆され, いわゆるクローム肺癌と考えたい. 発生部位は右S6末梢領域であり, 組織型は低分化腺癌であった. 本症例は発生部位, 組織型ともに従来報告のない肺野型低分化腺癌であり, 自然発生肺癌との鑑別に多くの問題を提起する症例と考えられる.

AN ADULT CASE OF THE PARALYTIC POLIOMYELITIS SYNDROME INDUCED BY COXSACKIE VIRUS TYPE A-2

麻痺性ポリオ症候群paralytic poliomyelitis syndromeは,その原因としてポリオウイルスが広く知られているが,他の腸管系ウイルスや,ムンプスウイルス,ヘルペスウイルスなどのウイルスによつても発症する.コクサッキーA群ウイルスによつて麻痺を呈する例は,比較的少なく,とくにA2型によると確定診断されたものは,本邦では報告がない.われわれは, 27才男性で,感冒様症状をもつて発症し,四肢の弛緩性麻痺および顔面神経,舌咽神経,迷走神経麻痺を呈し, 2カ月後には,ほぼ正常にまで回復した症例を経験した.原因にかんしては,血清学的にコクサッキーウイルスA2型に対する中和抗体価の有意の上昇を認め,さらに便,髄液中から同型ウイルスを同定し,コクサッキーウイルスA型によつて発症したものと診断した.