Serum adiponectin level is correlated with the size of HDL and LDL particles determined by high performance liquid chromatography.

OBJECTIVE: Adiponectin (APN) improves insulin resistance and prevents atherosclerosis, and HDL removes cholesterol from atherosclerotic lesions. We have demonstrated that serum HDL-cholesterol (HDL-C) and APN concentrations are positively correlated and that APN accelerates reverse cholesterol transport (RCT) by increasing HDL synthesis in the liver and cholesterol efflux from macrophages. We previously reported that APN reduced apolipoprotein (apo) B secretion from the liver. It is well-known that insulin resistance influences the lipoprotein profile. In this study, we investigated the clinical significance of APN levels and insulin resistance in lipoprotein metabolism. MATERIAL/METHOD: We investigated the correlation between serum APN concentration, HOMA-R, the lipid concentrations and lipoprotein particle size by high-performance liquid chromatography (HPLC) in 245 Japanese men during an annual health checkup. RESULTS: Serum APN level was positively correlated with the cholesterol content in large LDL and HDL particles, but inversely correlated with the cholesterol content in large VLDL and small LDL particles. HOMA-R was negatively correlated with the cholesterol content in large LDL and HDL particles and positively correlated with the cholesterol content in large VLDL and small LDL particles. By multivariate analysis, APN was correlated with the particle size of LDL-C and HDL-C independently of age, BMI and HOMA-R. CONCLUSIONS: APN may be associated with the formation of both HDL and LDL particles, reflecting the enhancement of RCT and the improvement in TG-rich lipoprotein metabolism and insulin resistance.

Serum apolipoprotein B-48 levels are correlated with carotid intima-media thickness in subjects with normal serum triglyceride levels.

BACKGROUND: Postprandial hyperlipidemia (PPHL) is an independent risk factor for coronary heart disease (CHD) which is based on the accumulation of chylomicrons (CM) and CM remnants containing apolipoprotein B-48 (apoB-48). Since atherosclerotic cardiovascular diseases are frequently observed even in subjects with normal serum triglyceride (TG) level, the correlation between fasting apoB-48 containing lipoproteins and carotid intima-media thickness (IMT) was analyzed in subjects with normal TG levels. METHODS: From subjects who took their annual health check at the Osaka Police Hospital (n=245, male), one-hundred and sixty-four male subjects were selected to take part in this study; the excluding factors were: systolic blood pressure ≥ 140 mmHg, intake of antihypertensive or antihyperlipidemic drugs, or age >65 years. The association between biochemical markers and IMT was analyzed and independent predictors of max-IMT were determined by multiple regression analysis in all subjects and in groups N-1 (TG<100mg/dl, n=58), N-2 (100 ≤ TG<150 mg/dl, n=53) and H (150 ≤ TG mg/dl, n=53), respectively. RESULTS: Fasting total cholesterol, LDL-cholesterol, HDL-cholesterol, apoB-100 and lnRemL-C (remnant lipoprotein-cholesterol) levels were not correlated with max-IMT, but lnTG and lnapoB-48 were significantly correlated with max-IMT in all subjects. LnapoB-48 and apoB-48/TG ratio were significantly correlated with max-IMT in group N-2. By multiple regression analysis, age and lnapoB-48 were independent variables associated with max-IMT in group N-2. CONCLUSION: Serum apoB-48 level might be a good marker for the detection of early atherosclerosis in middle-aged subjects with normal-range levels of blood pressure and TG.

The reduced expression and aberrant methylation of p16(INK4a) in chromate workers with lung cancer.

STUDY OBJECTIVES: It is known that chromium is one of the important inhaled carcinogens that cause lung cancer. Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). However, the epigenetic effects of chromium are not understood. MATERIALS AND METHODS: We investigated the methylation of the p16 gene using a methylation-specific PCR method in 30 chromate lung cancers and 38 non-chromate lung cancers, and the expression of the p16 protein using immunohistochemistry in 25 chromate lung cancers. RESULTS: Ten (33%) chromate lung cancers showed methylation of the p16 promoter region. On the other hand, 10 (26%) of the non-chromate lung cancers also showed it. The frequency of p16 methylation in non-chromate lung cancer was 0%, 33% and 30% for low (< or =600), moderate (<600, >1000) and high (> or =1000) Brinkman indexes, respectively. However, the frequency of p16 methylation in chromate lung cancer was constant, irrespective of the Brinkman index. In chromate lung cancer, patients with chromate exposure of less than 15 years never had p16 methylation, while 40% (> or =25 years) or 43% (> or =15, <25 years) of patients with chromate exposure of more than 15 years did. In chromate lung cancer, chromate exposure, not smoking, mainly influenced the p16 methylation. Most of the chromate lung cancers with p16 methylation (85.7%) showed repression of the p16 protein. CONCLUSIONS: We speculate that not only genetic but also epigenetic alterations are involved in the carcinogenesis due to chromium.

Microscopic analysis of the chromium content in the chromium-induced malignant and premalignant bronchial lesions of the rat.

OBJECTIVE: Our previous studies demonstrated that the frequency of gene instability in lung cancer of chromate workers was very high, but the frequencies of the p53 and ras gene mutations were low. To clarify the carcinogenesis of chromate in the lung, we established a chromate-induced cancer model in the rat proximal airway and examined the relationship between chromium accumulations and the chromium-induced cancer and premalignant bronchial lesions of the rat. METHODS: Fifteen male, bred, 12-week-old Jcl-Wister rats were used. A pellet of strontium chromate were inserted into the bronchus of the rats. The rats were sacrificed 9 months after the pellet was inserted. We pathologically examined the region of the bronchi to which the pellet was attached. We quantified the amount of chromium accumulation in the bronchial lesions using a microscopic X-ray fluorescence analyzer. RESULTS: Of the 15 rats, 1 rat had a lesion of squamous cell carcinoma (SCC), 7 rats had carcinoma in situ (CIS) or dysplasia, 8 rats had squamous metaplasia, and 5 rats had goblet cell hyperplasia. The amounts of chromium accumulation in normal epithelium (n=24), goblet cell hyperplasia (n=14), squamous metaplasia (n=8), and dysplasia plus CIS plus SCC (n=9) were 500+/-1354, 713+/-1062, 941+/-1328, and 3511+/-4473 (mean+/-SD) counts/s/mA, respectively. The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium (Spearman's correlation coefficient by ranks, rs=0.454, P<0.01). CONCLUSIONS: The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium. Examining the genetic alterations of histologic changes in this model was helpful in elucidating the process of carcinogenesis of chromium in the lung.

Matrix metalloproteinase inhibitor MMI-166 inhibits lymphogenous metastasis in an orthotopically implanted model of lung cancer.

Matrix metalloproteinases (MMP) are considered to be critically involved in tumor invasion and the metastasis of various cancers. MMI-166 is a selective inhibitor of matrix metalloproteinase (MMP-2, MMP-9, and MMP-14). The purpose of this study was to evaluate the effects of MMI-166 on both the growth of the implanted tumor and the lymph node metastasis of the mediastinum and prolonging the life span, using an orthotopic implantation model of the Ma44-3 cancer cell line. We examined the anti-invasive effect of MMI-166 in lung cancer cell lines using an in vitro invasion assay. Next, we examined the anticancer effect of MMI-166 in vivo. MMI-166 (200 mg/kg body weight) or a vehicle was administered orally to the orthotopically implanted lung cancer model. MMI-166 dose-dependently inhibited the invasion of cancer cell lines with expressions of MMP-2 and/or MMP-9 in vitro. In vivo, MMI-166 significantly inhibited mediastinal lymph node metastasis in this orthotopic model (weight of the mediastinum: control, 0.089 +/- 0.009 versus MMI-166, 0.069 +/- 0.008 mg; P = 0.005; metastatic area: control, 93,495 +/- 55,747 versus MMI-166, 22,747 +/- 17,478 pixels; P = 0.045). MMI-166 prolonged the life span by 6 days in median survival time in the orthotopically implanted model (P = 0.039). These results showed that MMI-166 could possibly inhibit lymph node metastasis and prolong the life span in lung cancer patients.

Myasthenia gravis appearing after thymectomy for thymoma.

OBJECTIVE: A few thymoma patients without myasthenia gravis (MG) have been observed to develop MG after total removal of the thymoma (postoperative MG). However, the cause of this is not yet known because of the rarity of postoperative MG patients. This study evaluated the clinical characteristics of the 8 postoperative MG patients. METHODS: We compiled 1089 thymoma patients treated between 1990 and 1994 in 115 institutes in Japan, and found 8 cases of postoperative MG. RESULTS: Postoperative MG was found in 8 (0.97%) of 827 thymoma patients without preoperative MG. The postoperative MG patients included 1 male and 7 females, with a mean age of 50.5+/-15.0 years. The thymoma was completely resected in all cases. The surgical method used was extended thymectomy in 2 cases and thymothymectomy in 6 cases. There were 2 cases (0.7%) of postoperative MG in the extended thymectomy group (n = 275), 6 (1.9%) in the thymothymectomy group (n = 321), and none in the tumor resection group (n = 137). The interval between thymectomy and the onset of postoperative MG varied (6 days-45 months, 19.3+/-16.5 months). The type of MG was ocular in 2 cases and general in 5 cases, according to the modified Osserman classification. The postoperative MG was responsive to anti-cholinesterase compounds and/or steroids. The improvement rate was 86%. CONCLUSIONS: Postoperative MG was present in about 1% of the patients who underwent total thymoma resection. Resection of the thymus gland does not prevent postoperative MG.

Thymidylate synthase and dihydropyrimidine dehydrogenase in non-small cell lung cancer: relationship between mRNA expression and activity.

BACKGROUND: UFT (Tegafur + Uracil) has been reported to be effective for postoperative adjuvant chemotherapy of non-small cell lung cancer (NSCLC) in a randomized prospective study. Recently, many clinical studies have demonstrated that UFT is effective for cancer with a low activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). In the present study, we investigated TS and DPD activity in resected tumors and corresponding normal lungs and the relationship between the activity and the mRNA expression of TS and DPD in NSCLC. MATERIALS AND METHODS: Seventy-seven patients underwent complete surgical resection and lymph node dissection for NSCLC. The activity of TS was determined by the FdUMP binding assay combined with gel filtration. The activity of DPD was determined by radio-enzymatic assay. Tumor tissues and their paired non-cancerous tissues were assayed. Furthermore, the mRNA expressions of TS and DPD were examined by real-time RT-PCR. RESULTS: The mean TS and DPD activities in NSCLC were approximately 2.4-fold and 5-fold of those in normal lungs. The mean TS and DPD activities of NSCLC were 0.099 pmol/mg and 407 pmol/mg/min, respectively. Although both TS and DPD activities showed a tendency to be high for adenocarcinoma, there was no significant difference between TS and/or DPD activities and any clinical findings (age, gender, stage and histological type). The mRNA expression of DPD was correlated with DPD activity (rs=0.846, p<0.001). The mRNA expression of TS was weakly correlated with TS activity (rs=0.757, p<0.001). CONCLUSION: TS and DPD activities in NSCLC were higher than those in normal lungs. Assay of DPD mRNA and TS mRNA by real-time RT-PCR can be used as an indicator for the use of UFT.

Thymoma and myasthenia gravis: a clinical study of 1,089 patients from Japan.

BACKGROUND: The thymus or thymoma plays a role in the pathogenesis of myasthenia gravis (MG). Although previous studies have reported that the presence of MG in thymoma patients is an indicator of poor prognosis, recent reports have shown that the presence of MG no longer influences the prognosis or indicates a more favorable prognosis in thymoma patients. METHODS: To clarify the difference in tumor behavior between thymoma with MG and that without MG, we compiled 1,089 thymomas treated between 1990 and 1994 from 115 institutes in Japan and analyzed the clinical characteristics of thymoma with MG compared with thymoma without MG. RESULTS: MG was associated with 270 cases (24.8%) of thymoma. The total resection cases comprised 94.6% and 91.4%, and the recurrent cases comprised 6.4% and 8.3% in the groups with and without MG, respectively. The 5-year survival rates for thymoma with and without MG in stage III were 85.7% and 89.3%, respectively; and those in stage IV were 85.1% and 63.9%, respectively. The prognosis of thymoma with MG in stage IV tended to be better than that of thymoma without MG (p = 0.0523). The thymoma with MG group had fewer stage IVb thymomas than did the thymoma without MG group (15% vs 34%). The resectability rate in the thymoma with MG group was higher than that in the thymoma without MG group (60% vs 38%). CONCLUSIONS: Thymoma with MG is equally or less malignant than that without MG. The infrequency of stage IVb thymomas and the high resectability rate had an influence on the favorable prognosis of stage IV thymoma with MG.

Microsatellite instability and protein expression of the DNA mismatch repair gene, hMLH1, of lung cancer in chromate-exposed workers.

Our previous studies of lung cancer in chromate-exposed workers (chromate lung cancer) have revealed that the frequency of replication error (RER) in chromate lung cancer is very high. We examined whether the RER phenotype of chromate lung cancer is due to an abnormality of DNA mismatch repair protein. We investigated the expression of a DNA mismatch repair gene, hMLH1, and hMSH2 proteins using immunohistochemistry and microsatellite instability (MSI) in 35 chromate lung cancers and 26 nonchromate lung cancers. Lung cancer without MSI or with MSI at one locus was defined as "RER(-)," lung cancer with MSI at two loci was defined as "RER(+)," and lung cancer with MSI at three or more loci was defined as "RER(++)." The repression rate of hMLH1 and hMSH2 proteins in chromate lung cancer was significantly more than that of nonchromate lung cancer (hMLH1: 56% vs. 20%, P = 0.006, hMSH2: 74% vs. 23%, P < 0.0001). In chromate lung cancer, the repression rate for hMLH1 was 43% in RER(-), 40% in RER(+), and 90% in the RER(++) group. The repression rate of hMLH1 protein in the RER(++) group was significantly higher than that in the RER(-) and RER(+) groups (P = 0.039). The inactivation of hMLH1 expression strongly correlated with the microsatellite high instability phenotype in chromate lung cancer. The genetic instability of chromate lung cancer is due to the repression of hMLH1 protein.

Determination of tamoxifen--DNA adducts in leukocytes from breast cancer patients treated with tamoxifen.

Tamoxifen (TAM), a widely used antiestrogen for breast cancer therapy and chemoprevention, increases the incidence of endometrial cancer in women. The formation of DNA adducts induced by tamoxifen may initiate endometrial cancer. To evaluate the genotoxic risk of TAM, the formation of DNA adducts in leukocytes was examined. Blood samples were collected from 47 breast cancer patients (61.7 +/- 12.5 years) taking TAM (20 mg/day; average duration until sampling, approximately 37 months) and 20 untreated patients (58.2 +/- 12.3 years), and their leukocyte DNA was analyzed by 32P-postlabeling/HPLC analysis. This assay resolves synthetic standards, trans- and cis-diastereoisomers of alpha-(N2-deoxyguanosinyl)tamoxifen 3'-monophosphate (dG3'P-N2-TAM), alpha-(N2-deoxyguanosinyl)-N-desmethyltamoxifen 3'-monophosphate (dG3'P-N2-N-dMeTAM), and alpha-(N2-deoxyguanosinyl)tamoxifen N-oxide 3'-monophosphate', and is capable of determining TAM adducts quantitatively. The detection limit of this assay is 0.6 adducts/10(9) nucleotides. trans-dG3'P-N2-TAM (fr-2; one of the two trans-isomers) was detected in six of 47 breast cancer patients treated with TAM. Among them, trans-dG(3'P-N2-N-dMeTAM (fr-2) was also detected in two patients. The total amounts of TAM-DNA adducts in the positive patients were 2.6 +/- 3.0 adducts/10(9) nucleotides. No adducts were detected in the controls. The presence of TAM-DNA adducts in the leukocyte DNA samples was confirmed using several 32P-postlabeling/HPLC systems.

Orthotopically implanted SCID mouse model of human lung cancer suitable for investigating metastatic potential and anticancer drug effects.

To evaluate the effects of drugs in clinical settings, an animal model of lung cancer similar to clinical cancer is necessary. Our previous studies described an SCID mouse model using orthotopic implantation of the human lung cancer cell line which mimicked the lymph node metastasis of patients with lung cancer. In this study, we made animal models that reflected various metastatic forms of lung cancer in humans. We applied our procedure to 6 lung cancer cell lines. Suspensions of 2.0 x 10(4) cancer cells were injected into the left lung of SCID mice. We evaluated the mRNA expressions of 52 proteins related to the metabolism of and resistance to anticancer drugs of each tumor cell line and its orthotopically implanted tumor using a customized cDNA array. Three lung cancer cell lines had the potential of lymphogenous metastasis and 3 cell lines had the potential of hematogenous metastasis in this model system. The A549 line showed multiple metastases, and Ma2 line showed solitary metastasis. The expression of 52 genes in each implanted tumor was closely correlated with that in each cell lines (correlation coefficients: 0.8883-0.9533), and the gradient of the regression line was more than 0.9. This model was similar to the metastatic form in patients with lung cancer. The similar expression of proteins in each tumor cell line in vitro and implanted tumor in vivo gives an advantage in evaluating the effects of molecular-targeted drugs and the relationship between specific genes and tumor potential in preclinical studies.

Novel bronchofiberscopic catheter spray device allows effective anesthetic spray and sputum suctioning.

STUDY OBJECTIVES: To evaluate how serum lidocaine concentrations (SLC) rise when lidocaine is administered by a Bronchofiberscopic Catheter Spray Device (BCSD), and to demonstrate the effect on the aspiration speed of a substitute for sputum when a catheter spray remains in the channel of the bronchofiberscope (BF). METHODS: This is a prospective randomized clinical study. After lidocaine ultrasonic nebulizer, the BF was inserted orally. During the procedure patients received 4% lidocaine by two methods. In Group 1, 11 patients received lidocaine by bronchofiberscopic (BF) injection. In Group 2, 15 patients received lidocaine by spraying from the diameter 1.06 mm catheter through the BF channel. SLC were measured at 40 min from onset of nebulization. Separately, we examined how effectively sputum was aspirated through the BF channel with a catheter. RESULTS: Total lidocaine dose (TLD) is the total dose used for nebulization and for the BF injection or spray. The TLD for Groups 1 and 2 were 698.2+/-162.1 mg (mean+/-SD) and 498.7+/-103.8 mg, respectively (P = 0.03). The SLC for Groups 1 and 2 were 1.28+/-0.72 and 1.48+/-0.70 mg/l, respectively (P = 0.49). CONCLUSIONS: Using BCSD allows easier in administration of lidocaine and is not associated with a significant increase in SLC in comparison with BF injection. Although sputum aspiration using the BF inserted with our catheter was somewhat slow, we did not feel inconvenient so much. Compared to the conventional method, using BCSD may be preferable for patients and bronchoscopists.

Green fluorescent protein expression and visualization of mediastinal lymph node metastasis of human lung cancer cell line using orthotopic implantation.

BACKGROUND: Suppression of lymphatic metastasis improves survival in lung cancer patients. We have reported a patient-like model of lung cancer metastasis based on orthotopic implantation in severe combined immunodeficiency (SCID) mice and demonstrated the lymphogenous spread histologically using human NSCLC cell lines. MATERIALS AND METHODS: To visualize micrometastases, we transfected the Aequorea Victoria jellyfish green fluorescent protein (GFP) gene to the cancer cell line. RESULTS: The tumor cell lines were able to stably express GFP at high levels both in vitro and in vivo. Fluorescent tumors and metastasis of the mediastinum could be visualized at microscopic levels after transplantation. CONCLUSION: This model demonstrated that GFP gene-transfected tumor cells represent a new tool for evaluating the metastatic process and are very useful for developing chemotherapy to inhibit metastasis.

WHO histologic classification is a prognostic indicator in thymoma.

BACKGROUND: The histologic classification of thymoma has remained a subject of controversy for many years. In 1999, the World Health Organization Consensus Committee published a histologic typing system for tumors of the thymus. METHODS: We reclassified a series of 100 thymomas resected at Tokushima University Hospital and four affiliated hospitals in Japan between 1973 and 2001 according to the World Health Organization histologic classification and reported its clinicopathologic relationship and prognostic relevance. RESULTS: There were 8 type A, 17 type AB, 27 type B1, 8 type B2, 12 type B3, and 28 type C thymomas. The frequency of invasion to neighboring organs increased according to tumor subtype in the order A (0%), AB (6%), B1 (19%), B2 (25%), B3 (42%), and C (89%). There was no recurrence in patients with type A, AB, or B2 thymoma. The recurrence rates of patients with B1, B3, or C thymoma were 15%, 36%, and 47%, respectively. The disease-free survival rates were 100% for types A and AB, 83% for types B1 and B2, 36% for type B3, and 28% for type C thymoma at 10 years. There were significant differences in disease-free survival between types A and AB and types B1 and B2 (p = 0.0436), and between type B3 and type C (p = 0.042). By multivariate analysis, only Masaoka clinical stage (p = 0.002) showed significant independent effects on disease-free survival. The 10-year survival rates of types A and AB, types B1 and B2, type B3, and type C thymoma were 100%, 94%, 92%, and 58%, respectively. CONCLUSIONS: The current study confirmed the World Health Organization histologic classification as a good prognostic factor.

Computed tomography-guided drainage for large pulmonary bullae.

Patients with large pulmonary emphysematous bullae often present therapeutic problems because of their poor respiratory function. We performed computed tomography (CT)-guided drainage in two patients with large pulmonary bullae who were considered poor surgical candidates. This method could be safely accomplished in a few minutes under local anesthesia and sufficient collapse of the bullae was obtained in both cases. We could control prolonged air leak from the catheter with bronchofiberoptic bronchial occlusion in one patient. CT-guided bulla drainage is a simple, speedy and minimally invasive treatment method for inoperable patients with large pulmonary bullae.

Lymphogenous and hematogenous metastasis of thymic epithelial tumors.

BACKGROUND: A TNM classification has been established for various tumors. However, the TNM classification of thymic epithelial tumor has not been established yet. METHODS: We received replies to a questionnaire on thymic epithelial tumors from 115 institutes. We compiled a database of 1,320 patients with thymic epithelial tumor (1,093 thymomas, 186 thymic carcinomas, and 41 thymic carcinoids) who were treated between 1990 and 1994. We used a tentative TNM classification of thymoma presented by Yamakawa and associates in 1991. The regional lymph nodes of the thymus were classified into three groups: anterior mediastinal lymph nodes (N1), intrathoracic lymph nodes (N2), and extrathoracic lymph nodes (N3). RESULTS: The rate of lymphogenous metastasis in thymoma, thymic carcinoma, and thymic carcinoid was 1.8%, 27%, and 28%, respectively. Most tumors with lymph node metastasis metastasized to N1 (thymoma, 90%; thymic carcinoma, 69%; thymic carcinoid, 91%). The 5-year survival rates of N0, N1, and N2 thymoma were 96%, 62%, and 20%, respectively. The 5-year survival rates of N0, N1(,) N2, and N3 thymic carcinoma were 56%, 42%, 29%, and 19%, respectively. The 5-year survival rates of M0 and M1 thymoma were 95% and 57%. The 5-year survival rates of M0 and M1 thymic carcinoma were 51% and 35%. Multivariate analysis demonstrated that survival of patients with thymoma was dependent on the clinical stage of Masaoka and complete resection. In thymic carcinoma, survival was dependent on lymph node metastasis and complete resection. CONCLUSIONS: The N factor was one of the predictors of survival in thymoma and thymic carcinoma. However, M factor showed less influence on survival than T or N factors.

Microscopic analysis of chromium accumulation in the bronchi and lung of chromate workers.

BACKGROUND: It is known that chromium is an inhaled carcinogen and an important risk factor in the development of lung carcinoma. METHODS: The authors used a microscopic X-ray fluorescence 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: 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 stroma but not in the epithelium. The maximum chromium accumulations in dysplasic (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). CONCLUSIONS: Previous studies found that lung carcinoma with chromate exposure exhibited a variety of genetic abnormalities. Considering genetic aberrations and chromium accumulation in these premalignant lesions is useful for elucidating the process of carcinogenesis in chromium-induced lung carcinoma.