Molecular and Histocytological Biomarkers - Ecological Biomarkers: Indicators of Ecotoxicological Effects - page 87

From blood

Ta rget cell

CH 2 OH

Retinol

Nucleus

CHO

Retinal

Corepressor

RAR RXR

COOH

atRA

Coactivator

RAR RXR

COOH

Expression of
target gene

13cRA 9cRA

RA response
element

COOH

Oxidative metabolites

Excretion

FIGURE 4.1
Schematic representation of the metabolism of retinoids. (After Inoue, D. et al., J. Health Sci ., 56, 221-230, 2010.
With permission.)

receptors, disruption of retinoid metabolism, or transport (Rolland 2000; Novák et al. 2008;
Inoue et al. 2010; Letcher et al. 2010; Chen et al. 2012). They include alkylphenolic com-
pounds with various alkyl groups, pesticides, polychlorinated dioxins, polychlorinated
biphenyls, polybrominated diphenyl ethers, polycyclic aromatic compounds, and other
organic pollutants as well as environmental complex mixtures such as pulp mill-pro-
duced compounds or contaminated sediment extracts.
Retinol was proposed as a biomarker of contaminant-related toxicity as early as 2000
in marine mammals (Simms and Ross 2000). However, Simms and Ross recommended a
cautionary approach to avoid misinterpretations associated with the effects of confounding
factors. A recent paper by Routti et al. (2010) reinforces this recommendation since it showed
that contaminant levels and their relationships with physiological or endogenous variables
can be highly confounded by molting/fasting status. The sampling matrix must also be
chosen adequately, as demonstrated by Bechshøft et al. (2011), who have shown that retinol
was not uniformly distributed in the kidney of polar bears ( Ursus maritimus ). Despite these
limitations, associations between blubber PCB concentrations and plasma retinol concentra-
tions as well as concentrations of stored retinol in blubber were established in harbor seals
( Phoca vitulina ) from the Pacific coast of British Columbia (Canada) and Washington state
(USA) (Mos et al. 2007). According to these authors, retinol concentrations and retinoic acid
receptor α (RARα) expression levels can therefore represent relevant and sensitive biomark-
ers of PCB-associated toxic effects in toxicological studies of marine mammals. In ringed
seals ( Phoca hispida baltica ) and gray seals ( Halichoerus grypus ) living in the multipolluted