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KMID : 0366919960080010051
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Sungkyun Pharmceutical Journal
1996 Volume.8 No. 1 p.51 ~ p.64
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COMPARATIVE ASSESSMENT OF DNA ADDUCT FORMATION, SALMONELLA MUTAGENICITY, AND CHROMOSOME ABERRATION ASSAYS AS SHORT-TERM TESTS FOR DNA DAMAGE
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Choi, Myung Ja
Lee, Jung Wha/Lee, Byung Mu
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Abstract
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DNA adduct formation assay (DAFA) was carried out to compare dose responses with the Ames test and chromosomal aberration test using aflatoxin B_1 (AFB_1) and benzo[a]pyrene (BaP). In the bacterial mutation test, AFB_1 and BaP (-01) ㎍/plate) were all positive in TA97a and TA100 with dose-related revertants. However, the slopes of the dose-response curves were gradual (slope 0.55-3.73, r=.84-.98). In the chromosome aberration test, a significant increase in the percentage of chromosomal aberrations was obtained from male ICR mouse spleen cells treated with AFB_1 and BaP, but a dose-related increase was insensitive (slope 0.09-0.23, r=.75-.78). The incidence of chromosomally aberrant spleen cells treated with BaP was significantly increased compared with AFB_1. DAFA was performed in vitro with [^3H]-AFB_1 and [^3H]BaP. These two carcinogens were able to induce genotoxicity and showed good dose-related increases in terms of DNA dduct formation (slope 0.78-1.28, r=1.00). Coefficients of variation (CV) for the slope of each dose-response curve were much lower in DAFA in vitro (CV 15.09-18.34%) than those in any other test (CV 19.69-99.33%), Ames test; 18.89-45.58%, chromosome aberration test). furthermore, DFA in vivo was performed to investigate organotropic DNA adduct formation and persistence in Sprague-Dawley rats ip or orally treated with AFB_1 and BaP. DNA adducts were monitored for 48-96 h by enzyme-linked immunosorbent assay (ELISA) using corresponding monoclonal antibodies, 6A10 and 8E11. DAFA in vivo demonstrated that the liver and kidney might be the probably target organs for AFB_1 with the highest formation and persistence of DNA adducts and the lung and liver for BaP regardless of the route of administration. The results suggest that DAFA in vitro could be useful for detecting genotoxic compounds, and DAF in vivo should also be considered as a good alternative method for the screening of organ-specific chemical carcinogens.
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