Page 716 - The Toxicology of Fishes

696 The Toxicology of Fishes

Heme
NADPH + O 2

Heme oxygenase
(HSP30)
3+
CO + Fe + NADP +
Biliverdin
NADPH

Biliverdin reductase

NADP +

Bilirubin
FIGURE 16.5 Degradation pathway of heme.

metabolism through a mechanism involving interaction of CYP1A with the halogenated aromatic com-
pound potentially initiating oxidative stress (Hahn and Chandran, 1996). Based on the relationships
between HSP30 (oxygenase), CYP1A (protein), bilirubin, and biliverdin (endogenous Ah agonists) (see
Figure 16.5), assessment of porphyrin profiles may provide significant mechanistic insight when they
are measured with these other proteins and metabolites. It is obvious that the use of these metabolites
as biomarkers has been largely overlooked in fish and deserves further characterization.

Retinoids
Vitamin A-derived compounds, also known as retinoids, are an additional group of endogenous metab-
olites that have shown promise as biomarkers of effect and potential exposure to planar halogenated
aromatic compounds when used in combination with other markers (Alsop et al., 2005; Arcand Hoy et.
al. 1999; Peakall, 1992; Spear et al., 1992). In brook trout (Salvelinus fontinalis), a single injection of
5 µg/g of a coplaner PCB (3,3′,4,4′-TCBP) reduced retinoids in several tissues (Ndayibagira et al., 1995).
In the same study, lake sturgeon (Acipenser fulvescens) collected from a contaminated waterway near
Montreal, Canada, had significantly lower retinoid levels in the intestine. In addition, field studies with
white sucker demonstrated a direct relationship between maternal retinoid loss, CYP1A activity in the
liver, and prevalence of embryonic malformations in animals collected from the same contaminated
location, with significant gender-related differences in hepatic retinoid expression (Branchaud et al.,
1995). Following a chronic exposure of 3 years to PAH-contaminated sediment in a mesocosm, retinol
concentrations in plasma and liver were significantly reduced in Atlantic flounder (Besselink et al., 1998).
In fact, a negative, nonlinear correlation was found between retinol concentrations and CYP1A expres-
sion, indicating that retinoids may be a significant indicator of exposure and effect of planar aromatic
compounds or other Ah receptor ligands (Alsop et al., 2005). Due to the meager research efforts directed
toward retinoid metabolism and disposition in fish, the relationships between altered hepatic retinoid
levels and fish health are uncertain; however, given the prominent role of retinoids in cellular metabolism
and development, relationships appear likely and deserve further study.

Genotoxic Endpoints
Alterations to an organisms’ genetic material (DNA) represent an impact of the highest order. The
consequences of DNA alterations potentially affect all levels of biological organization, from the molec-
ular to community level. Of central importance to an organism are its survival and reproductive success.
Neither is attainable without maintaining the integrity of its genetic material, DNA. At the molecular
level, the corruption of the information coded in DNA may not pass beyond the boundary of an affected