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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

Mitochondrial and nuclear DNA damage in killifish larvae 4 days after repeated 24-hr exposures to DMSO vehicle or BaP (100 or 200 μg/L). Frequency of lesions in (A) KC larvae and (B) ER larvae. KC larvae showed a significant increase in relative lesion frequency in both mitochondrial and nuclear DNA after exposure to 200 μg/L BaP (p ≤ 0.001). The ER larvae showed no significant increase in either mitochondrial or nuclear DNA lesion frequency for any of the concentrations of BaP examined; ER vehicle controls showed a significantly higher level of mitochondrial DNA lesion frequency than KC larvae (p < 0.05). Data are mean lesion frequency ± SEM; n = 4 pools of two larvae per treatment group.**p < 0.001 compared with control by Bonferroni-corrected ANOVA.
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f2-ehp-118-1376: Mitochondrial and nuclear DNA damage in killifish larvae 4 days after repeated 24-hr exposures to DMSO vehicle or BaP (100 or 200 μg/L). Frequency of lesions in (A) KC larvae and (B) ER larvae. KC larvae showed a significant increase in relative lesion frequency in both mitochondrial and nuclear DNA after exposure to 200 μg/L BaP (p ≤ 0.001). The ER larvae showed no significant increase in either mitochondrial or nuclear DNA lesion frequency for any of the concentrations of BaP examined; ER vehicle controls showed a significantly higher level of mitochondrial DNA lesion frequency than KC larvae (p < 0.05). Data are mean lesion frequency ± SEM; n = 4 pools of two larvae per treatment group.**p < 0.001 compared with control by Bonferroni-corrected ANOVA.

Mentions: Using LA-QPCR we detected a significant increase in lesion frequency in both nuclear and mitochondrial DNA in KC larvae 4 days after repeated 24-hr exposure to 200 μg/L BaP (p < 0.001) (Figure 2A). This increased DNA damage was significantly higher in mitochondrial DNA than in nuclear DNA (p < 0.001), but we observed no significant increase in DNA damage in KC larvae after exposure to 100 μg/L BaP. ER larvae had a higher basal level of mitochondrial lesion frequency; however, no significant change in DNA damage was observed after exposure to either 100 or 200 μg/L BaP (Figure 2B).


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)

Mitochondrial and nuclear DNA damage in killifish larvae 4 days after repeated 24-hr exposures to DMSO vehicle or BaP (100 or 200 μg/L). Frequency of lesions in (A) KC larvae and (B) ER larvae. KC larvae showed a significant increase in relative lesion frequency in both mitochondrial and nuclear DNA after exposure to 200 μg/L BaP (p ≤ 0.001). The ER larvae showed no significant increase in either mitochondrial or nuclear DNA lesion frequency for any of the concentrations of BaP examined; ER vehicle controls showed a significantly higher level of mitochondrial DNA lesion frequency than KC larvae (p < 0.05). Data are mean lesion frequency ± SEM; n = 4 pools of two 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

f2-ehp-118-1376: Mitochondrial and nuclear DNA damage in killifish larvae 4 days after repeated 24-hr exposures to DMSO vehicle or BaP (100 or 200 μg/L). Frequency of lesions in (A) KC larvae and (B) ER larvae. KC larvae showed a significant increase in relative lesion frequency in both mitochondrial and nuclear DNA after exposure to 200 μg/L BaP (p ≤ 0.001). The ER larvae showed no significant increase in either mitochondrial or nuclear DNA lesion frequency for any of the concentrations of BaP examined; ER vehicle controls showed a significantly higher level of mitochondrial DNA lesion frequency than KC larvae (p < 0.05). Data are mean lesion frequency ± SEM; n = 4 pools of two larvae per treatment group.**p < 0.001 compared with control by Bonferroni-corrected ANOVA.
Mentions: Using LA-QPCR we detected a significant increase in lesion frequency in both nuclear and mitochondrial DNA in KC larvae 4 days after repeated 24-hr exposure to 200 μg/L BaP (p < 0.001) (Figure 2A). This increased DNA damage was significantly higher in mitochondrial DNA than in nuclear DNA (p < 0.001), but we observed no significant increase in DNA damage in KC larvae after exposure to 100 μg/L BaP. ER larvae had a higher basal level of mitochondrial lesion frequency; however, no significant change in DNA damage was observed after exposure to either 100 or 200 μg/L BaP (Figure 2B).

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