Relationship between formation of carcinogen-DNA adducts [CA] and micronuclei [MN] in mouse keratinocytes exposed to carcinoges.
Toxicologist 1995 Mar; 15(1):81
This project is concerned with determining the relationship between two biological markers of exposure [CA and MN] in viable keratinocytes following exposure to an environmental and occupational carcinogen; 7H-dibenzo[c,g]carbazole [DBC], in comparison to the carcinogen-7, 12 dimethylbenz[a]anthracene [DMBA]. Mouse keratinocytes were grown on collagen coated dishes [CA analysis] and slides [MN analysis] and dosed with the carcinogen. The dishes were trypsinized and the cells kept frozen at -80°C for subsequent DNA isolation and CA analysis [32 P-postlabelling]. The medium for the cells grown on slides was replaced with medium containing cytochalasin-B (drug which blocks cytokinesis 3 j,tglml) and the cells were cultured for 72 hours, then fixed in 100% methanol and stained with acridine orange. DBC induced a dose-dependent [10-1000 ngtml] increase in MN [36.2-105.8 MN/1000 binucleated [BN] cells] over solvent controls [32 +/- 3.7; N = 3] and in CA [10.9-37 (Relative Adduct Labelling [RAL] x 107 nucleotides) over solvent controls [5.7 +/- 2.9 (RAL x 107 nucleotides); N = 4]. DMBA induced a dose-dependent [32-256 ng/ml] increase in MN [46.6110.1 MN/l000 BN cells] over solvent controls [21.3 +/- lQ.4; N = 3]. DMBAinduced CA [3.5-10.8 (RAL x 107 nucleotides)] were very low when compared to solvent controls [2.4 +/- 0.7; N = 3]. The results indicate that the relationship between MN frequency and CA formation is unique for each compound tested.
Exposure-assessment; Cell-morphology; Cell-transformation; Animal-studies; Laboratory-animals; Cancer; Carcinogens; DNA-adducts; Biomarkers
The Toxicologist. Society of Toxicology 34th Annual Meeting, March 5-9,1995, Baltimore, Maryland