Mj. Choi et al., COMPARATIVE-ASSESSMENT OF DNA ADDUCT FORMATION, SALMONELLA MUTAGENICITY, AND CHROMOSOME ABERRATION ASSAYS AS SHORT-TERM TESTS FOR DNA-DAMAGE, Journal of toxicology and environmental health, 49(3), 1996, pp. 271-284
DNA adduct formation assay (DAFA) was carried out to compare dose resp
onses with the Ames test and chromosomal aberration test using aflatox
in B-1 (AFB(1)) and benzo[a]pyrene (BaP). In the bacterial mutation te
st, AFB(1) and BaP (0-1 mu g/plate) were all positive in TA97a and TA1
00 with dose-related revertants. However, the slopes of the dose-respo
nse curves were gradual (slope 0.55-3.73, r =.84-.98). in the chromoso
me aberration test, a significant increase in the percentage of chromo
somal aberrations was obtained from male ICR mouse spleen cells treate
d with AFB(1) and BaP, but a dose-related increase was insensitive (sl
ope 0.09-0.23, r.75-.78). The incidence of chromosomally aberrant sple
en cells treated with BaP was significantly increased compared with AF
B(1). DAFA was performed in vitro with [H-3]-AFB(1) and [(PH)-P-3]BaP.
These two carcinogens were able to induce genotoxicity and showed goo
d dose-related increases in terms of DNA adduct 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; 18.89-44.58
%, chromosome aberration test). Furthermore, DAFA in vivo was performe
d to investigate organotropic DNA adduct formation and persistence in
Sprague-Dawley rats ip or orally treated with AFB, and BaP. DNA adduct
s were monitored for 48-96 h by enzyme-linked immunosorbent assay (ELI
SA) using corresponding monoclonal antibodies, 6A10 and 8E11. DAFA in
vivo demonstrated that the liver and kidney might be the probable targ
et organs for AFB, with the highest formation and persistence of DNA a
dducts and the lung and liver for BaP regardless of the route of admin
istration. The results suggest that DAFA in vitro could be useful for
detecting genotoxic compounds, and DAFA in vivo should also be conside
red as a good alternative method for the screening of organ-specific c
hemical carcinogens.