DNA interactions and bacterial mutagenicity of some chromium(III) imine complexes and their chromium(V) analogues. Evidence for chromium(V) intermediates in the genotoxicity of chromium(III)
Ct. Dillon et al., DNA interactions and bacterial mutagenicity of some chromium(III) imine complexes and their chromium(V) analogues. Evidence for chromium(V) intermediates in the genotoxicity of chromium(III), AUST J CHEM, 53(5), 2000, pp. 411-424
The in vitro DNA interactions and bacterial mutagenicities of cis-[Cr-III(p
hen)(2)(OH2)(2)](3+) and trans-[Cr-III(salen)(OH2)(2)](+) and their Cr-V an
alogues are reported. At pH 3.3, cis-[Cr(phen)(2)(OH2)(2)](3+) (0.02-2.0 mM
) causes negatively supercoiled pUC9 DNA to smear on agarose gels, with sub
stantial precipitation in the well at greater than or equal to 1.0 mM. Much
weaker interactions between Cr-III and DNA were apparent at pH 7.4. The in
teractions between DNA and Cr-V phen complexes (0.5 mM total Cr, pH 3.3) ge
nerated by oxidation of cis-[Cr(phen)(2)(OH2)(2)](3+) (for 10-30 min) resul
ted in almost complete nicking of form I DNA to forms II and III DNA. Nicki
ng of form I DNA (greater than or equal to 80%) was also apparent at pH 7.4
following reaction of DNA with PbO2-oxidized [Cr(phen)(2)(OH2)(2)](3+) (2
mM Cr). Interactions between trans-[Cr-III(salen)(OH2)(2)](+) and DNA were
weaker than those of the Cr-III phen complex at both pH 3.3 and 7.4. The Cr
-V salen derivative (0.5 mM total Cr) caused the disappearance of form I DN
A at oxidation times of greater than or equal to 10 min and at pH 3.3 with
substantial cleavage. While oxidation of [Cr(salen)(OH2)(2)](+) by PbO2 was
not observed at pH 7.4, the complex was oxidized by iodosobenzene to produ
ce short-lived [CrO(salen)](+) that caused DNA smearing on the agarose gel.
In bacterial mutagenicity assays, the Cr-III imine complexes and their Cr-
V analogues produced similar mutagenic responses, which were believed to be
due to the instabilities of the Cr-V species in the bacterial growth mediu
m. While the spectrum of the mutagenic activities differed between the chro
mium phen and salen complexes, both exhibited greatest mutagenicity in Salm
onella typhimurium TA102. These data suggest that Cr-V species, generated i
n vivo by cellular oxidative enzymes, may be responsible for Cr-III-induced
mutagenesis.