Page 558 - The Toxicology of Fishes

538 The Toxicology of Fishes

Aflatoxins O O Alkylating Agents
Me2N–NO
O
Dimethylnitrosamine
O
O OMe
Aflatoxin B1

Polycyclic Aromatic Hydrocarbons

Benzo(a)pyrene

Aromatic Amines
NH 2

Naphthylamine

H N NH 2
2
Benzidine
FIGURE 12.2 Common classes of environmental contaminants that act as initiating agents.

aromatic amines (Figure 12.2), for each of which examples concerning development of cancers in fish
have been reported. A short discussion of potential new classes of chemical carcinogens then follows.
Aflatoxins are fungal toxins produced by species such as Aspergillus flavus that grow on grain and
peanut crops in humid conditions. Aflatoxins are a major contributory cause of human liver cancer in
the tropics, mainly as a result of ingesting contaminated foods. Fish, particularly trout, have been
experimentally exposed to these compounds in their role as a surrogate for humans in examining the
toxicological effects (Bailey et al., 1998; Tilton et al., 2005). Trout are selected due to their well-
documented sensitivity to aflatoxin B (AFB ), and channel catfish are often selected as a comparatively
1
1
resistant species. Fish used in aquaculture, including tilapia and channel catfish, have also been the
subject of aflatoxin studies, primarily to investigate the effect of contaminated foodstuff (Lim et al.,
2001; Manning et al., 2005).
Polycyclic aromatic hydrocarbons (PAHs) are the pyrolysis products of fossil fuels such as oil, coal,
tobacco smoke, and grilled meat. Benzo(a)pyrene (BaP) is frequently used as a model carcinogen,
although the most potent carcinogenic hydrocarbons in mammalian models are actually 7,12-dimethyl-
benzanthracene (DMBA) and dibenzo(a,l)pyrene (DBP). All are involved in the genesis of major cancers
in mammals but are not in themselves carcinogenic; they act instead as promoting agents after biotrans-
formation. Laboratory studies have begun to investigate the causal relationship between a number of
PAHs and neoplasia in a number of fish species. Research has involved tank-held fish and exposures to
defined chemicals, including BaP, DMBA, DBP, and chemical mixes of various PAHs, to investigate the
role and mechanism of PAH-induced cancer in fish (Rotchell et al., 2001a). Such studies aim to address
progression in terms of histopathology but also describe specific molecular-level changes occurring
during tumor development.
Aromatic amines are used in the dye and rubber industries. Examples include β-/α-naphthylamine,
now banned because of their role in human bladder cancer, and dimethylaminobenzene, a food dye used
to color margarine which is also banned because of its role in causing liver and bladder cancers in
humans. Nitrosamines are a third class; these are procarcinogens that require enzymatic activation to