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.
Takahashi
Yuji
Y
Department of Oncological and Regenerative Surgery, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima 770-8503, Japan.
Kondo
Kazuya
K
Ishikawa
Sumiyo
S
Uchihara
Hiroshi
H
Fujino
Haruhiko
H
Sawada
Naruhiko
N
Miyoshi
Takanori
T
Sakiyama
Shoji
S
Izumi
Keisuke
K
Monden
Yasumasa
Y
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
D002840:Chromates; D002857:Chromium; C048629:strontium chromate; D013324:Strontium