The correlation between DNA adducts and chromosomal aberrations in the target organ of benzidine exposed, partially-henatectomized mice.
Talaska G; Au WW; Ward JB Jr.; Randerath K; Legator MS
Carcinogenesis 1987 Dec; 8(12):1899-1905
The correlation between DNA adducts and chromosomal aberrations was studied in the liver of benzidine (92875) exposed male ICR-Sprague- Dawley-mice after partial hepatectomy. Mice underwent partial hepatectomy, treatment with benzidine (0, 7.8, 19.5, 38.2, or 97.8mg/kg, intraperitoneally), and subcutaneous implantation of a 50 milligram 5-bromodeoxyuridine tablet at 58 hours. Intraperitoneal injection of colcemid (0.04 milligrams per 10 grams body weight) was administered at 70 hours. At 72 hours, mice were killed by cervical dislocation and the livers were removed and subjected to adduct analysis and cytogenic study. No chromosome type aberrations were observed. The majority of damage detected was observed as chromatid breaks. The results demonstrated a clastogenic effect for benzidine in-vivo. Relative adduct labeling (RAL) values were determined and a clear dose response relationship, linear for the dose range tested, was observed. Correlation between chromosomal aberration rate and net RAL was determined. The correlation coefficient for individual mice was 0.41 with a considerable scatter of individual points. Four outlying cases from the set contributed significantly to the variability of data. When the four points were removed, the correlation coefficient was 0.74. The authors conclude that benzidine/DNA adducts are associated with chromosomal aberrations in- vivo, corroborating the findings on associations between in-vitro mutagenesis and transformation and levels of particular carcinogen DNA adducts. Results indicated that DNA adduct levels may be important predictive factors in genotoxicity, including neoplasia.
NIOSH-Publication; NIOSH-Grant; In-vitro-studies; In-vivo-studies; Laboratory-animals; Liver-cells; Carcinogenesis; Liver-tumors; Genetic-factors
Prev Med and Community Health University of Texas 301 University Boulevard Galveston, TX 77550
University of Texas Medical Branch, Galveston, Texas