|Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
To compare carcinogenic effects on human lung between asbestos fibers and tobacco smoke in terms of genesis of adenocarcinoma, we examined LOH frequency (presented by FAL values) and p53 mutation in 137 lung adenocarcinomas, for which asbestos burden (AB, asbestos body numbers per unit dry lung tissue) was measured using paraffin blocks of normal lung tissue. At first, tissues of primary lung adenocarcinomas (n=46) resected in 1990's were used. The cases were divided into three groups based on mean asbestos body concentrations (AB) (numbers per g of lung (dry)) as follows AB null (AB =0; n=22), AB low (0<AB<1000; n=14).and AB high (AB>=1000; n=11). Differentiation grades of adenocarcinoma (well-(WD)/moderately-(MD)/poorly-(PD)) were 6/11/4 in AB null,6/8/0 in AB low, and 4/7/0 in AB high group. LOH frequency was 0.17 in AB null, 0.07 in AB low and 0.13 in AB high groups. p53 mutations were detected in 12 cases (27%). The frequency of the mutation significantly correlated with AB degree
(16% (3/19) in AB null, 29% (4/14) in AB low, and 45% (5/11) in AB high group, p=0.006). Secondary, in the 4 groups (Group 1: AB =0, SI =0, Group 2: AB>0, SI =0, Group 3: AB =0, SI>0, Group 4 AB>0, SI>0), FAL was the highest in Group 4 and low in the other 3 groups. p53 mutation frequency increased sequentially from Group 1 (21%) to Group 4 (50%). Smoking related mutations such as colon 273 and transversions were often seen in Groups 3 and 4 but occasionally also in Groups1 and 2. No asbestos specific mutations were identified. Asbestos didn't change proportion of well/moderately/poorly diff. adenocarcinomas. Poorly-differentiate adenocarcinoma, usually seen in smokers, was found in 4 patients (F:M=3:1) of Group 1.
These findings showed (1) combined effects of cigarette smoke and asbestos were evident in terms of LOH frequency and p53 mutation status, (2) asbestos seems to promote malignant progression of cells injured by genotoxic agents such as tobacco smoke rather than it injures genes by itself, because it doesn't increase LOFT frequency, (3) possibly, poorly-diff. adenocarcinoma, not related to smoking, exists, and (4) smoking-related mutations seen in non-smokers are deemed due to passive smoking. Less