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Comparative chronic liver toxicity of benzo[a]pyrene in two populations of the atlantic killifish (Fundulus heteroclitus) with different exposure histories.

Wills LP, Jung D, Koehrn K, Zhu S, Willett KL, Hinton DE, Di Giulio RT - Environ. Health Perspect. (2010)

Bottom Line: However, adult ER killifish show a greater prevalence of hepatic and pancreatic tumors compared with those from reference sites.CYP1A activity was induced by BaP in KC but not ER larvae, and KC larvae demonstrated a greater reduction in whole-body concentrations of BaP over time.In addition to acquiring the heritable resistance to the acute teratogenic effects of PAHs, ER fish appear to have concomitantly developed resistance to chronic effects, including cancer.

View Article: PubMed Central - PubMed

Affiliation: Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, USA.

ABSTRACT

Background: The Atlantic Wood Industries Superfund site on the Elizabeth River (ER) in Portsmouth, Virginia, is contaminated with polycyclic aromatic hydrocarbons (PAHs) derived from creosote. Embryos and larvae of ER killifish (Fundulus heteroclitus) are refractory to the induction of enzymes regulated by the aryl hydrocarbon receptor including cytochrome P4501A (CYP1A) and are resistant to PAH-induced lethality and teratogenicity. However, adult ER killifish show a greater prevalence of hepatic and pancreatic tumors compared with those from reference sites.

Objectives: We used controlled laboratory studies to determine if ER killifish are more or less sensitive to PAH-induced chronic hepatic toxicity than killifish from an uncontaminated site.

Methods: Larvae from the ER and a reference site on King's Creek (KC) were subjected to two 24-hr aqueous exposures of benzo[a]pyrene (BaP; 0-400 µg/L). At various time points, larvae were analyzed for CYP1A activity, BaP concentrations, nuclear and mitochondrial DNA damage, and liver pathology.

Results: CYP1A activity was induced by BaP in KC but not ER larvae, and KC larvae demonstrated a greater reduction in whole-body concentrations of BaP over time. Mitochondrial and nuclear DNA lesion frequency increased significantly in BaP-exposed KC larvae, but not in ER larvae. Nine months postexposure, KC juveniles exhibited significantly more hepatic foci of cellular alteration and only KC juveniles developed hepatocellular carcinomas.

Conclusions: In addition to acquiring the heritable resistance to the acute teratogenic effects of PAHs, ER fish appear to have concomitantly developed resistance to chronic effects, including cancer.

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Related in: MedlinePlus

Effect of BaP in KC and ER killifish larvae after laboratory exposure to either the DMSO vehicle (control) or BaP (10–200 μg/L). (A) Induction of CYP1 enzymatic activity measured in larvae by the in vitro EROD assay 4 days after repeated 24-hr BaP exposures. Data are mean ± SEM; n = 4 pools of 10 larvae per treatment group. (B) BaP extracted and identified by UPLC/MS 24, 48, and 96 hr after 24 hr exposure to 100 μg/L BaP. The dashed line represents the detection limit. Effects of population, treatment, and time on the recovery of BaP were significant (p < 0.05; ANOVA), with more BaP recovered from the ER larvae than from KC larvae. The interaction of population and time was significant (p < 0.001), with the KC larvae showing a greater reduction in whole-body concentration of BaP over time than the ER larvae. No BaP was detected in the vehicle control larvae. Data are mean concentration of BaP recovered per 10 larvae ± SEM; n = 5 pools of 10 larvae per treatment group.**p < 0.001 compared with control by Bonferroni-corrected ANOVA.
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f1-ehp-118-1376: Effect of BaP in KC and ER killifish larvae after laboratory exposure to either the DMSO vehicle (control) or BaP (10–200 μg/L). (A) Induction of CYP1 enzymatic activity measured in larvae by the in vitro EROD assay 4 days after repeated 24-hr BaP exposures. Data are mean ± SEM; n = 4 pools of 10 larvae per treatment group. (B) BaP extracted and identified by UPLC/MS 24, 48, and 96 hr after 24 hr exposure to 100 μg/L BaP. The dashed line represents the detection limit. Effects of population, treatment, and time on the recovery of BaP were significant (p < 0.05; ANOVA), with more BaP recovered from the ER larvae than from KC larvae. The interaction of population and time was significant (p < 0.001), with the KC larvae showing a greater reduction in whole-body concentration of BaP over time than the ER larvae. No BaP was detected in the vehicle control larvae. Data are mean concentration of BaP recovered per 10 larvae ± SEM; n = 5 pools of 10 larvae per treatment group.**p < 0.001 compared with control by Bonferroni-corrected ANOVA.

Mentions: Consistent with previous studies, laboratory-reared larval killifish from parents of the KC population exhibited significant induction of CYP1A enzymatic activity 4 days after repeated 24-hr exposures to 10–200 μg/L BaP (p < 0.001) (Figure 1A), whereas ER killifish exhibited no significant induction.


Comparative chronic liver toxicity of benzo[a]pyrene in two populations of the atlantic killifish (Fundulus heteroclitus) with different exposure histories.

Wills LP, Jung D, Koehrn K, Zhu S, Willett KL, Hinton DE, Di Giulio RT - Environ. Health Perspect. (2010)

Effect of BaP in KC and ER killifish larvae after laboratory exposure to either the DMSO vehicle (control) or BaP (10–200 μg/L). (A) Induction of CYP1 enzymatic activity measured in larvae by the in vitro EROD assay 4 days after repeated 24-hr BaP exposures. Data are mean ± SEM; n = 4 pools of 10 larvae per treatment group. (B) BaP extracted and identified by UPLC/MS 24, 48, and 96 hr after 24 hr exposure to 100 μg/L BaP. The dashed line represents the detection limit. Effects of population, treatment, and time on the recovery of BaP were significant (p < 0.05; ANOVA), with more BaP recovered from the ER larvae than from KC larvae. The interaction of population and time was significant (p < 0.001), with the KC larvae showing a greater reduction in whole-body concentration of BaP over time than the ER larvae. No BaP was detected in the vehicle control larvae. Data are mean concentration of BaP recovered per 10 larvae ± SEM; n = 5 pools of 10 larvae per treatment group.**p < 0.001 compared with control by Bonferroni-corrected ANOVA.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2957915&req=5

f1-ehp-118-1376: Effect of BaP in KC and ER killifish larvae after laboratory exposure to either the DMSO vehicle (control) or BaP (10–200 μg/L). (A) Induction of CYP1 enzymatic activity measured in larvae by the in vitro EROD assay 4 days after repeated 24-hr BaP exposures. Data are mean ± SEM; n = 4 pools of 10 larvae per treatment group. (B) BaP extracted and identified by UPLC/MS 24, 48, and 96 hr after 24 hr exposure to 100 μg/L BaP. The dashed line represents the detection limit. Effects of population, treatment, and time on the recovery of BaP were significant (p < 0.05; ANOVA), with more BaP recovered from the ER larvae than from KC larvae. The interaction of population and time was significant (p < 0.001), with the KC larvae showing a greater reduction in whole-body concentration of BaP over time than the ER larvae. No BaP was detected in the vehicle control larvae. Data are mean concentration of BaP recovered per 10 larvae ± SEM; n = 5 pools of 10 larvae per treatment group.**p < 0.001 compared with control by Bonferroni-corrected ANOVA.
Mentions: Consistent with previous studies, laboratory-reared larval killifish from parents of the KC population exhibited significant induction of CYP1A enzymatic activity 4 days after repeated 24-hr exposures to 10–200 μg/L BaP (p < 0.001) (Figure 1A), whereas ER killifish exhibited no significant induction.

Bottom Line: However, adult ER killifish show a greater prevalence of hepatic and pancreatic tumors compared with those from reference sites.CYP1A activity was induced by BaP in KC but not ER larvae, and KC larvae demonstrated a greater reduction in whole-body concentrations of BaP over time.In addition to acquiring the heritable resistance to the acute teratogenic effects of PAHs, ER fish appear to have concomitantly developed resistance to chronic effects, including cancer.

View Article: PubMed Central - PubMed

Affiliation: Nicholas School of the Environment, Duke University, Durham, North Carolina 27708, USA.

ABSTRACT

Background: The Atlantic Wood Industries Superfund site on the Elizabeth River (ER) in Portsmouth, Virginia, is contaminated with polycyclic aromatic hydrocarbons (PAHs) derived from creosote. Embryos and larvae of ER killifish (Fundulus heteroclitus) are refractory to the induction of enzymes regulated by the aryl hydrocarbon receptor including cytochrome P4501A (CYP1A) and are resistant to PAH-induced lethality and teratogenicity. However, adult ER killifish show a greater prevalence of hepatic and pancreatic tumors compared with those from reference sites.

Objectives: We used controlled laboratory studies to determine if ER killifish are more or less sensitive to PAH-induced chronic hepatic toxicity than killifish from an uncontaminated site.

Methods: Larvae from the ER and a reference site on King's Creek (KC) were subjected to two 24-hr aqueous exposures of benzo[a]pyrene (BaP; 0-400 µg/L). At various time points, larvae were analyzed for CYP1A activity, BaP concentrations, nuclear and mitochondrial DNA damage, and liver pathology.

Results: CYP1A activity was induced by BaP in KC but not ER larvae, and KC larvae demonstrated a greater reduction in whole-body concentrations of BaP over time. Mitochondrial and nuclear DNA lesion frequency increased significantly in BaP-exposed KC larvae, but not in ER larvae. Nine months postexposure, KC juveniles exhibited significantly more hepatic foci of cellular alteration and only KC juveniles developed hepatocellular carcinomas.

Conclusions: In addition to acquiring the heritable resistance to the acute teratogenic effects of PAHs, ER fish appear to have concomitantly developed resistance to chronic effects, including cancer.

Show MeSH
Related in: MedlinePlus