Cytotoxicity and apoptosis-inducing activity of bisphenol A and hydroquinone in HL-60 cells.
BPA (bisphenol A or 2,2-bis(4-hydroxy-phenol)propane) and hydroquinone (HQ, 1,4-benzenediol) are present in dental resin materials, and small quantities of these substances may be eluted from the resins. Recently, attention has focused on the estrogen-like and carcinogenic adverse effects of BPA and HQ. Thus, it is important to investigate the cytotoxicity and apoptosis-inducing activity of these compounds. BPA and HQ reduced the viable cell number of human promyelocytic leukemia (HL-60), human oral squamous cell carcinoma (HSC-2) and human submandibular gland (HSG) cell lines in a concentration-dependent manner. The cytotoxic activity of HQ, but not of BPA, was significantly reduced by the addition of N-acetyl-L-cysteine (NAC). In biomimetic studies of the prooxidant/antioxidant activity of thiols during oxidation of BPA or HQ, the radical-scavenging activities of mixtures of BPA or HQ and 2-mercapto-1-methylimidazole (MMI, a thiol) were investigated by the induction period method. BPA without MMI showed a higher induction period (antioxidant activity) than did HQ, but BPA with MMI did not cause oxygen uptake. In contrast, HQ with MMI caused oxygen uptake, suggesting formation of MMI thiyl radicals during oxidation of HQ followed by reaction with molecular oxygen. This indicates that HQ may produce intracellular reactive oxygen species (ROS) and provides an explanation for the decrease in the cytotoxicity of HQ by NAC. BPA induced internucleosomal DNA fragmentation, a biochemical marker of apoptosis, only in HL-60 cells. BPA activated caspase-9 and caspase-3, suggesting induction of apoptosis via caspase activation by the caspase recruitment domain. The cytotoxicity of BPA was 2-fold less than that of HQ, whereas the apoptosis-inducing activity of BPA was 10-fold less than that of HQ.
Terasaka
Hiroshi
H
Department of Oral Diagnosis, Meikai University School of Dentistry, Saitama, Japan.
Kadoma
Yoshinori
Y
Sakagami
Hiroshi
H
Fujisawa
Seiichiro
S
D000111:Acetylcysteine / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001559:Benzhydryl Compounds; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D006873:Hydroquinones / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D009707:Nucleosomes / Q000187:drug effects; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects; D000098826:Bisphenol A Compounds
D000111:Acetylcysteine; D000975:Antioxidants; D001559:Benzhydryl Compounds; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D016166:Free Radical Scavengers; D006873:Hydroquinones; D007093:Imidazoles; D009707:Nucleosomes; D010636:Phenols; D017382:Reactive Oxygen Species; C107674:2-mercapto-1-methylimidazole; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C031927:hydroquinone