Effects of germanium oxide and other chemical compounds on phenylmercury acetate-induced genotoxicity in cultured human lymphocytes.
Phenylmercury acetate (PMA), which not only causes an elevation of sister chromatid exchanges (SCEs) but also induces high frequency of endoreduplication in human lymphocytes, may be genotoxic to humans. The major aim of our study was to investigate the effects of germanium oxide (GeO2), D-penicillamine (D-PA), dimercaprol (BAL), and diltiazem (DTM) on PMA-induced genotoxicity as quantified by SCEs. All concentrations of the four chemical compounds tested alone did not induce genotoxicity in cultured human lymphocytes. However, GeO2 significantly inhibited PMA-induced genotoxicity in a concentration-dependent manner. Similarly, D-PA at concentrations of 3 microM and 10 microM, and BAL at a concentration of 30 microM produced the antigenotoxic effects. In addition, GeO2 (1.5 microM) significantly reversed an increase of endoreduplication frequency caused by PMA. In a cell cycle kinetic study, GeO2 (0.5-5.0 microM) reversed the inhibition of PMA on the proliferating rate index (PRI) of lymphocytes. On the contrary, both D-PA and DTM at concentrations of 30-300 microM markedly potentiated PMA-induced inhibition of PRI. These findings show that GeO2, D-PA and BAL could antagonize PMA-induced genotoxicity, and GeO2 appears to be the most effective.
Lee
C H
CH
Department of Pharmacology, Chung Shang Medical and Dental College, Taichung, Taiwan.
Lin
R H
RH
Liu
S H
SH
Lin-Shiau
S Y
SY
D000328:Adult; D000931:Antidotes / Q000008:administration & dosage / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology; D004112:Dimercaprol / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005659:Fungicides, Industrial / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity*; D005857:Germanium / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D016685:Mitomycin / Q000494:pharmacology / Q000633:toxicity; D016296:Mutagenesis / Q000187:drug effects / Q000235:genetics; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology / Q000633:toxicity; D010396:Penicillamine / Q000008:administration & dosage / Q000494:pharmacology; D010662:Phenylmercuric Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000235:genetics
D000931:Antidotes; D016587:Antimutagenic Agents; D002121:Calcium Channel Blockers; D005659:Fungicides, Industrial; D019384:Nucleic Acid Synthesis Inhibitors; D005857:Germanium; D004112:Dimercaprol; D016685:Mitomycin; C040516:germanium oxide; D004110:Diltiazem; D010396:Penicillamine; D010662:Phenylmercuric Acetate