Page 567 - The Toxicology of Fishes

Chemical Carcinogenesis in Fishes 547

A O
O
HN
N
HN
N
OH·
NH 2
N ONOO·
N NH 2 OH
N
N
Guanine

O

HN
N
HN 2 OH
N
N
8-Hydroxyguanine H

B O
O
HN
N HN
N
NH 2 N ONOO·
N NH 2 N NO 2
N

Guanine 8-Nitroguanine

–
FIGURE 12.6 (A) Hydroxyl radical (OH·)- and peroxynitrite (ONOO )-mediated oxidation of guanine. (B) Peroxynitrite
–
(ONOO )-mediated nitration of guanine to form 8-nitroguanine.
exposure concentrations. Likewise, Malins and colleagues (1990) examined DNA from neoplastic livers
of feral English sole exposed to carcinogens. Concentrations of the guanine-derived lesion, 2,6-diamino-

4-hydroxy-5-formamido-pyrimidine (FapyGua), ranged from 0.97 to 5.11 nmol/mg DNA. FapyGua was

notdetected in non-neoplastic tissue, and this study suggested that reactive oxygen species damageDNA

in living systems and thus may play an important role in the formation of neoplastic tissue. In fact,
concentrations of 8-oxo-dG in tissues have also been adopted as a biomarker of oxidative stress and
environmental pollution in several species of fish including English sole (Malins and Haimanot, 1991),
Sparus aurata (Rodriguez-Ariza et al., 1999), and Anguilla anguilla (Machella et al., 2005).
Chemical–Viral Interactions
Many strains of DNA tumor viruses are known to cause several types of cancer in mammalian models.
Also, an estimated 20% of human cancers are thought to have a viral component in their etiology. Human
papilloma virus (HPV), for example, can cause intraepithelial neoplasias, or abnormal and precancerous