Genetic analyses of bronchogenic, carcinoma arising in ex-chromate workers : researches on sequential change of bronchial dysplastic changes and autopsy cases.

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Chromate workers are well known to be a high-risk group for developing lung cancers and provide a good model for bronchial carcinogenesis. We investigated expression of cell cycle regulatory proteins (p53, MDM2, p21, p14, p16, cyclin D1 and RB) immunohistochemically and loss of heterozygosity (LOH) in chromate induced squamous cell carcinomas (SCCs), compared with those in lung cancers from nonexposed individuals. Of 7 chromate-induced lung cancer, abnormal expression of p53, MDM2, p21, p14, p16, cyclin D1 and RB were 71%, 43%, 100%, 0%, 71%, 29% and 0%, respectively. In contrast, of 10 SCCs from nonexposed individuals were 80%, 40%, 100%, 10%, 60%, 30% and 20%, respectively. The frequency of expression of these proteins proved to be not significant between chromate-induced SCCs and the comparison group. Then, we examined LOH in 7 lung cancers from chromate-exposed workers and in 10 comparison cases without chromate exposure, using 7 microsatellite markers : D3S1300 (3p), C13 1107 (3p), D5S644 (5q), D9S171(9p), mfd220 (9q), RBi2 (13q) and TP53(17p). The 6 cases out of chromate-exposed workers were informative, whereas all the cases were informative in the comparison group. The frequency of LOH at 3p, 3p, 5q, 9p, 9q, 13q and 17p loci in tumors with chromate exposure.was not significantly different from that in tumors without chromate exposure. These findings suggest that the carcinogenic mechanisms of chromate lung cancer may not differ from that of non-chromate lung cancer.