Chemistry Reference
In-Depth Information
OR
OR
O
P
O-
O
P
O-
H
B
B
O
B
O
Cr(V)-ehba
O
O
O
2
H
H
H
H
H
H4'
H
H
H
H
H
H
O
O
O
O
P
O-
O
P
O-
Base
propenal
OR
OR
+
OR
O
P
O-
O
O
O
glycolic acid termini
Figure 17.10
Abstraction of the C4
hydrogen by Cr(V)-ehba leads to formation of a base
propenals and frank strand scission
88,91
′
was assigned based on the formation of deoxyribose oxidation products of base
propenals, glycolic acid (Figure 17.10) and, like the C1
mechanism, gives rise to
frank DNA strand breaks
57,88,89,91
Also, much like the Cr(V)-BT model complex,
Cr(V)-ehba has shown the ability to interact with phosphates to position the oxidiz-
ing metal towards the site of oxidation (the C4
′
hydrogen atom of deoxyribose).
92
Single-strand breaks, such as those initiated by abstraction of a C4
′
hydrogen by Cr(V) and/or Cr(IV) species, are one of the most common genetic
lesions reported following exposure to Cr(VI).
45
Single - strand breaks have been
shown to cause base deletions,
93
as well as gross chromosomal damage
94
including
sister chromatid exchanges
47 - 49
and micronuclei formation.
45
The gross chromosomal
damage that has been observed in cells exposed to Cr(VI) has led to the labelling
of hexavalent chromium compounds as clastogenic in addition to their classifi cation
as carcinogens. Another lethal downstream effect of single-strand breaks are double-
strand breaks created when a replication fork encounters a single-strand break and
collapses.
96
Based on the literature of Cr(VI)-induced single-strand breaks, it is
apparent that rapid repair of these breaks is necessary to avoid genotoxicity.
′
or C1
′
17.3.2 Repair of Deoxyribose Oxidation Products
Single-strand breaks occur frequently, even when a cell has not been exposed to a
genotoxin and are in fact thought to be the most common type of genetic lesion.
95
