Chemistry Reference
In-Depth Information
O
N
NH
N
N
NH
10
R
HO
9
8
HO
7
OH
Attachment of BP 7,8-diol 9,10-oxide
to guanine residue of DNA
fIgure 9.3
DNA adduct formation.
“bay region epoxides” have a strong tendency to form DNA adducts (see Hodgson
and Levi 1994) .
There is strong evidence that DNA adduction by these bulky reactive metabolites
of PAHs is far from random, and that there are certain “hot spots” that are preferen-
tially attacked. Differential steric hindrance and the differential operation of DNA
repair mechanisms ensure that particular sites on DNA are subject to stable adduct
formation (Purchase 1994). DNA repair mechanisms clearly remove many PAH/
guanine adducts very quickly, but studies with P
32
postlabeling have shown that cer-
tain adducts can be very persistent—certainly over many weeks. Evidence for this
has been produced in studies on fish and
Xenopus
(an amphibian; Reichert et al.
1991; Waters et al. 1994).
Although genotoxicity is of central importance in human toxicology, its signifi-
cance in ecotoxicology is controversial. However, PAH has been shown to cause
tumor development in fish in response to, for example, oral, dermal, or intraperito-
neal administration of benzo[
a
]pyrene and 3-methyl cholanthrene. Hepatic tumors
have been reported in wild fish exposed to sediment containing about 250 mg/kg of
PAH (Environmental Health Criteria 202). K-ras mutations occurred in pink salmon
embryos (
Onchorhynchus gorbuscha
) following exposure to crude oil from the
tanker
Exxon Valdez
, which caused extensive pollution of coastal regions of Alaska
(Roy et al. 1999). However, it is not clear whether cancer is a significant factor in
determining the survivorship or reproductive success of free-living vertebrates or
invertebrates. Cancers usually take a long time to develop, and the life span of free-
living animals is limited by factors such as food supply, disease, predation, etc. Do
they live long enough for cancers to be a significant cause of population decline?
Apart from carcinogenicity, there is the wider question of other possible genotoxic
effects in free-living animals, effects that may be heritable if the mutations are in
germ cells. Studying aquatic invertebrates exposed to PAH, Kurelec (1991) noticed a
number of longer-term physiological effects, which he termed collectively
genotoxic
disease syndrome
. Although the basis for these effects has not yet been elucidated,
the observations raise important questions that should be addressed. PAHs have been
shown to form a variety of adducts in fish and amphibians, so there is a strong suspi-
cion that some of these may lead to the production of mutations. If mutations occur
Search WWH ::
Custom Search