title: Microscopic analysis of the chromium content in the chromium-induced malignant and premalignant bronchial lesions of the rat.
abstract: 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.
authors.affiliation: Department of Oncological and Regenerative Surgery, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima 770-8503, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kondo
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchihara
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Fujino
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Sawada
authors.forename: Takanori
authors.initials: T
authors.lastname: Miyoshi
authors.forename: Shoji
authors.initials: S
authors.lastname: Sakiyama
authors.forename: Keisuke
authors.initials: K
authors.lastname: Izumi
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Monden
mesh_terms: D000818:Animals; D001980:Bronchi / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D002283:Carcinoma, Bronchogenic / Q000139:chemically induced* / Q000737:chemistry / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000737:chemistry / Q000473:pathology; D002840:Chromates; D002857:Chromium / Q000032:analysis / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology; D006965:Hyperplasia; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000737:chemistry / Q000473:pathology; D008297:Male; D008679:Metaplasia; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D012720:Severity of Illness Index; D013194:Staining and Labeling; D013324:Strontium
chemical_list: D002840:Chromates; D002857:Chromium; C048629:strontium chromate; D013324:Strontium