Mutagenicity of N-OH-MOCA (4-amino-4'-hydroxylamino-bis-3,3'-dichlorodiphenylmethane) and PBQ (2-phenyl-1,4-benzoquinone) in human lymphoblastoid cells.
The genotoxic potential of two occupationally significant chemicals, 4,4'-methylene-bis-2-chloroaniline (MOCA) and 2-phenyl-1,4-benzoquinone (PBQ), was explored by monitoring the induction of mutations at the HPRT locus of AHH-1 human lymphoblastoid cells. Exposure of AHH-1 cells to the putative carcinogenic metabolite of MOCA, N-OH-MOCA, induced a 6-fold increase in mutant frequency and resulted in base pair substitutions primarily at A:T base pairs. In contrast, exposure to PBQ did not result in an increased mutant frequency although this compound was significantly more cytotoxic than N-OH-MOCA at equimolar doses. The induction of mutations at A:T sites by N-OH-MOCA is consistent with the type of DNA damage known to be produced by MOCA and provides a specific marker of genotoxic damage for exposed populations.
Reid
T M
TM
Division of Biomedical and Behavioral Sciences, National Institute for Occupational Safety and Health, Cincinnati, OH 45226, USA. tar9@cdc.gov
DeBord
D G
DG
Cheever
K L
KL
Savage
R E
RE
D016227:Benzoquinones / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000032:analysis / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology*; D008753:Methylenebis(chloroaniline) / Q000031:analogs & derivatives* / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D016227:Benzoquinones; D002273:Carcinogens; D009153:Mutagens; C029322:phenylbenzoquinone; D008753:Methylenebis(chloroaniline); D004247:DNA; C044313:5-hydroxy-3,3'-dichloro-4,4'-diaminodiphenylmethane-5-sulfate; D007041:Hypoxanthine Phosphoribosyltransferase