Induction of sister-chromatid exchanges by 2-aminofluorene in cultured human lymphocytes with and without erythrocytes.
2-Aminofluorene (2-AF), an indirect mutagen reported to be metabolically activated by erythrocytes in the Salmonella mutagenicity test, was studied for the induction of sister-chromatid exchanges (SCEs) in human lymphocytes in vitro with (whole-blood cultures) and without erythrocytes (isolated lymphocyte cultures). 2-AF (0.025-0.8 mM) was present in the cultures for the last 48 h of 72-h cultures. In both types of culture, SCEs increased in a dose-dependent manner, with a statistically significant elevation already at the lowest concentration of 2-AF tested and maximum responses of 2.4-fold (whole blood) and 2.1-fold (isolated lymphocytes), in comparison with mean SCEs/cell in control cultures, at 0.4 and 0.2 mM concentrations (respectively). Thus, the induction of SCEs by 2-AF was not dependent on the presence of erythrocytes. Styrene (2 mM), a positive control chemical known to require erythrocytes for efficient SCE induction in vitro, was shown to produce a 4.9-fold increase in SCEs in whole-blood cultures, but only a slight (1.3-fold) effect in isolated lymphocyte cultures. The results suggest that leukocytes, but not erythrocytes, are important in the metabolic activation of 2-AF in the human lymphocyte SCE assay.
Norppa
H
H
Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland.
Järventaus
H
H
D000328:Adult; D001711:Biotransformation; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism*; D005449:Fluorenes / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D012854:Sister Chromatid Exchange
D005449:Fluorenes; D009153:Mutagens; C012177:2-aminofluorene