The in vitro DNA interactions and bacterial
mutagenicities of
cis-[CrIII(phen)2(OH2)2]3+
and
trans-[CrIII(salen)(OH2)2]+
and their CrV analogues 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 substantial precipitation in the well at ≥1.0 mM. Much weaker
interactions between CrIII and DNA were apparent at pH
7.4. The interactions between DNA and CrV phen complexes
(0.5 mM total Cr, pH 3.3) generated by oxidation of
cis-[Cr(phen)2(OH2)2]3+
(for 10–30 min) resulted in almost complete nicking of form I DNA to
forms II and III DNA. Nicking of form I DNA (≥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-[CrIII(salen)(OH2)2]+
and DNA were weaker than those of the CrIII phen complex
at both pH 3.3 and 7.4. The CrV salen derivative (0.5 mM
total Cr) caused the disappearance of form I DNA at oxidation times of ≥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 produce short-lived
[CrO(salen)]+ that caused DNA smearing on
the agarose gel. In bacterial mutagenicity assays, the
CrIII imine complexes and their
CrV analogues produced similar mutagenic responses,
which were believed to be due to the instabilities of the
CrV species in the bacterial growth medium. While the
spectrum of the mutagenic activities differed between the chromium phen and
salen complexes, both exhibited greatest mutagenicity in
Salmonella typhimurium TA102. These data suggest that
CrV species, generated in vivo by
cellular oxidative enzymes, may be responsible for
CrIII-induced mutagenesis.
Role of the supX gene in ultraviolet light-induced mutagenesis in Salmonella typhimurium.
