revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY 288
2. HEALTH EFFECTS
mercuric chloride. In a study of the potentiating effects of organomercurials on clastogen-induced
chromosomal aberrations in cultured Chinese hamster cells, Yamada et al. (1993) investigated the effects of
five organomercurial compounds (methylmercuric chloride, ethylmercuric chloride, phenylmercuric
chloride, dimethylmercury, and diethylmercury) and found all to produce remarkable cytotoxicity. Fifty
percent or more depression in the mitotic index was observed following treatment with methylmercuric
chloride (2.5 µg/mL), ethylmercuric chloride (2.5 µg/mL), phenylmercuric chloride (1.25 µg/mL), and HgCl
and HgCl2 ($1.25 µg/mL). Post-treatment with methylmercuric chloride and ethylmercuric chloride
increased the number of breakage and exchange-type aberrations induced by 4-nitroquinoline 1-oxide and
methylmethane sulfonate but they did not show any clastogenic effects by themselves. Dimethylmercury,
diethylmercury, mercurous chloride, and mercuric chloride did not show any potentiating effects. Following
pretreatment with the 4-nitroquinoline 1-oxide or the DNA cross-linking agent mitomycin C, treatment with
methylmercuric chloride during the G1 phase resulted in the enhancement of both breakage- and exchangetype
aberrations. Ethylmercuric chloride treatment during the G1 phase also enhanced both types of
aberrations induced by 4-nitroquinoline 1-oxide, but did not show any potentiating effect. When treatment
was during the G2 phase, however, both methylmercuric chloride and ethylmercuric chloride enhanced
breakage-type aberrations only. In the Yamada et al. (1993) study, the dialkyl mercury compounds
dimethylmercury and diethylmercury did not show any cytotoxicity at 5–40 µg/mL, but they did cause a
significant increase in the frequency of aberrant cells at the 40 µg/mL concentration. The authors of this
study suggested three possible mechanisms for the observed potentiation of clastogenicity by monoalkylated
mercurials: (1) they interfere with the repair of base lesions induced by 4-nitroquinoline 1-oxide and
mitomycin C during the prereplication stage, thus increasing unrepaired DNA lesions that subsequently
convert into DNA double-strand breaks in the S phase; (2) methylmercuric chloride (but not ethylmercuric
chloride) inhibits the repair of cross-linking lesions during the prereplication stage; and (3) their G2 effects
enhance breakage-type aberrations only. Yamada et al. (1993) concluded that because mercury compounds
are known to react with protein thiol groups to inhibit protein activity, it is possible that they also inhibit
some protein activities involved in the DNA repair process. The specific target protein for organomercurials
and why the potentiation activities of methylmercury chloride and ethylmercury chloride differ remain to be
identified.
There is a sizable database of studies investigating the DNA-damaging activity of mercuric chloride. The
finding that mercuric chloride can damage DNA in rat and mouse embryo fibroblasts (Zasukhina et al.
1983), supports the in vivo evidence of species- and intraspecies-specific sensitivity to the genotoxic action
of mercuric chloride. Marked conversion of DNA into the single-stranded form occurred at 10 -6 M