An evaluation of 6 chromosomal mutagens in the AS52/XPRT mutation assay utilizing suspension culture and soft agar cloning.
The AS52/XPRT mutation assay was examined for sensitivity in the detection of chromosomal mutagens. 6 compounds identified as chromosomal mutagens in the mouse lymphoma assay (MLA) were tested for mutagenicity in AS52 cells using suspension treatment and soft agar cloning. The 6 compounds were benzo[a]pyrene (BAP), 2-acetylaminofluorene (2AAF), methylmethanesulfonate (MMS), methyl acrylate (MCR), benzoin (BZ), and p-aminophenol (AM). BAP, 2AAF and MMS were mutagenic. The mutagenic responses for BAP, 2AAF and MMS included small colony mutants which have been shown to correlate with chromosomal mutation in the MLA. Colonies ranged from approximately 0.2 to 1.5 mm in size. The mutant frequency (MF) for the AS52 cells treated with BAP and 2AAF exceeded that previously reported for the MLA by 2-fold. In contrast, the MF for AS52 cells treated with MMS was one-third that reported in the MLA. The MF obtained in AS52 cells exceeded that reported for the CHO/HGPRT mutation assay for all 3 compounds. MCR, which produces almost entirely small colonies in the MLA, was negative in AS52 cells as were the MLA chromosomal mutagens AM and BZ. However, AM and BZ have only been reported mutagenic in the MLA. Both are considered nongenotoxic and noncarcinogenic. The results with the latter 3 compounds suggest that the AS52 assay is not as sensitive as the MLA for the detection of compounds identified as chromosomal mutagens.
Oberly
T J
TJ
Toxicology Research Laboratories, Lilly Research Laboratories, Division of Eli Lilly and Company, Greenfield, IN 46140.
Huffman
D M
DM
Scheuring
J C
JC
Garriott
M L
ML
D015073:2-Acetylaminofluorene / Q000633:toxicity; D000179:Acrylates / Q000633:toxicity; D000627:Aminophenols / Q000633:toxicity; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D001573:Benzoin / Q000633:toxicity; D002460:Cell Line; D003001:Cloning, Molecular; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008741:Methyl Methanesulfonate / Q000633:toxicity; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D012680:Sensitivity and Specificity
D000179:Acrylates; D000627:Aminophenols; D009153:Mutagens; D001564:Benzo(a)pyrene; D015073:2-Acetylaminofluorene; D008741:Methyl Methanesulfonate; D007041:Hypoxanthine Phosphoribosyltransferase; D001573:Benzoin; C035956:methyl acrylate