Potentiating effects of organomercuries on clastogen-induced chromosome aberrations in cultured Chinese hamster cells.
Mercury compounds are among the most serious environmental pollutants. In this communication, the potentiating effects of organic and inorganic mercuries on clastogen-induced chromosome aberrations were studied in Chinese hamster CHO K1 cells. Post-treatment with monoalkylated mercuries--methyl mercuric chloride (MeHgCl) and ethyl mercuric chloride (EtHgCl)--increased the number of breakage- and exchange-type aberrations induced by 4-nitroquinoline 1-oxide (4NQO) and methyl methanesulfonate. With the DNA crosslinking agents mitomycin C (MMC) and cisplatin, MeHgCl enhanced both types of aberrations while EtHgCl enhanced breakage-type aberrations only. Since these monoalkylated mercuries did not show clastogenic effects by themselves under the present experimental conditions, the increases in chromosome aberrations were not additive. Dialkylated mercuries (dimethyl mercury and diethyl mercury) and inorganic mercuries (HgCl and HgCl2) did not show any potentiating effects. When MMC- or 4NQO-treated cells were post-treated with MeHgCl during the G1 phase, both breakage- and exchange-type aberrations were enhanced. Treatment with EtHgCl during the G1 phase also enhanced both types of aberrations induced by 4NQO. With MMC, however, G1 treatment with EtHgCl did not show any potentiating effect. MeHgCl and EtHgCl treatments during the G2 phase enhanced breakage-type aberrations only. Based on these results, the following possible mechanisms for potentiation of clastogenicity by monoalkylated mercuries were suggested; (1) they interfere with repair of base lesions induced by 4NQO and MMS during the pre-replicational stage, thereby increasing unrepaired DNA lesions which convert into DNA double-strand breaks in S phase, (2) MeHgCl (but not EtHgCl) also inhibits repair of crosslinking lesions during the pre-replicational stage, and (3) their G2 effects enhance breakage-type aberrations only.
Yamada
H
H
Faculty of Pharmaceutical Science, Toyama Medical and Pharmaceutical University, Japan.
Miyahara
T
T
Kozuka
H
H
Matsuhashi
T
T
Sasaki
Y F
YF
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000818:Animals; D016466:CHO Cells; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004357:Drug Synergism; D005034:Ethylmercuric Chloride / Q000633:toxicity; D005035:Ethylmercury Compounds / Q000633:toxicity; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D008767:Methylmercury Compounds / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D009941:Organomercury Compounds / Q000633:toxicity*; D010663:Phenylmercury Compounds / Q000633:toxicity
D005035:Ethylmercury Compounds; D008767:Methylmercury Compounds; D009153:Mutagens; D009941:Organomercury Compounds; D010663:Phenylmercury Compounds; C007378:diethylmercury; D015112:4-Nitroquinoline-1-oxide; D004247:DNA; C073972:dimethyl mercury; D005034:Ethylmercuric Chloride; C004925:methylmercuric chloride; C008859:phenylmercuric chloride