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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

Photomicrographs H&E-stained paraffin sections showing liver pathology (FCA) in KC killifish juveniles 9 months after exposure to DMSO (vehicle control; A) or 400 μg/L BaP (B–D). (A) Normal liver from a vehicle control. (B) Focal steatosis in liver from a BaP-exposed killifish; the arrow indicates large rounded vacuoles with smooth margins signifying lipid. (C) Eosinophilic foci (EF) in liver from a BaP-exposed killifish. (D) Hepatocellular carcinoma in liver from a BaP-exposed killifish; the arrow indicates an irregular and invasive border of the carcinoma. Bars = 100 μm.
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f4-ehp-118-1376: Photomicrographs H&E-stained paraffin sections showing liver pathology (FCA) in KC killifish juveniles 9 months after exposure to DMSO (vehicle control; A) or 400 μg/L BaP (B–D). (A) Normal liver from a vehicle control. (B) Focal steatosis in liver from a BaP-exposed killifish; the arrow indicates large rounded vacuoles with smooth margins signifying lipid. (C) Eosinophilic foci (EF) in liver from a BaP-exposed killifish. (D) Hepatocellular carcinoma in liver from a BaP-exposed killifish; the arrow indicates an irregular and invasive border of the carcinoma. Bars = 100 μm.

Mentions: We observed no FCA, adenomas, or hepatic neoplasms in KC or ER larvae exposed to DMSO, and no lesions were found in any juveniles 3 months after exposure to BaP (50, 100, 200, or 400 μg/L) (data not shown). Nine months after dosing, 2 of the 25 KC juveniles exposed to 200 μg/L BaP developed eosinophilic FCA, denoting an 8% incidence in lesion frequency; however, this was not significantly different from DMSO controls (Figure 3). Of the 30 KC juveniles exposed to 400 μg/L BaP, 9 developed increased FCA (Figure 3); of these 9 juveniles, 2 also developed early hepatocellular adenomas, and 1 developed a hepatocellular carcinoma (Figure 4D). These observations denoted a 30% incidence in lesion frequency that was significantly different from the DMSO control (p = 0.026). Only 2 of the 30 ER juveniles dosed with 400 μg/L BaP developed eosinophilic FCA, resulting in a 6% incidence in lesion frequency; this was not significantly different from controls. KC juveniles exposed to 400 μg/L BaP exhibited a significantly greater lesion frequency than similarly exposed ER juveniles (p = 0.018). No hepatocellular adenomas or carcinomas were found in the ER juveniles that we examined.


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)

Photomicrographs H&E-stained paraffin sections showing liver pathology (FCA) in KC killifish juveniles 9 months after exposure to DMSO (vehicle control; A) or 400 μg/L BaP (B–D). (A) Normal liver from a vehicle control. (B) Focal steatosis in liver from a BaP-exposed killifish; the arrow indicates large rounded vacuoles with smooth margins signifying lipid. (C) Eosinophilic foci (EF) in liver from a BaP-exposed killifish. (D) Hepatocellular carcinoma in liver from a BaP-exposed killifish; the arrow indicates an irregular and invasive border of the carcinoma. Bars = 100 μm.
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f4-ehp-118-1376: Photomicrographs H&E-stained paraffin sections showing liver pathology (FCA) in KC killifish juveniles 9 months after exposure to DMSO (vehicle control; A) or 400 μg/L BaP (B–D). (A) Normal liver from a vehicle control. (B) Focal steatosis in liver from a BaP-exposed killifish; the arrow indicates large rounded vacuoles with smooth margins signifying lipid. (C) Eosinophilic foci (EF) in liver from a BaP-exposed killifish. (D) Hepatocellular carcinoma in liver from a BaP-exposed killifish; the arrow indicates an irregular and invasive border of the carcinoma. Bars = 100 μm.
Mentions: We observed no FCA, adenomas, or hepatic neoplasms in KC or ER larvae exposed to DMSO, and no lesions were found in any juveniles 3 months after exposure to BaP (50, 100, 200, or 400 μg/L) (data not shown). Nine months after dosing, 2 of the 25 KC juveniles exposed to 200 μg/L BaP developed eosinophilic FCA, denoting an 8% incidence in lesion frequency; however, this was not significantly different from DMSO controls (Figure 3). Of the 30 KC juveniles exposed to 400 μg/L BaP, 9 developed increased FCA (Figure 3); of these 9 juveniles, 2 also developed early hepatocellular adenomas, and 1 developed a hepatocellular carcinoma (Figure 4D). These observations denoted a 30% incidence in lesion frequency that was significantly different from the DMSO control (p = 0.026). Only 2 of the 30 ER juveniles dosed with 400 μg/L BaP developed eosinophilic FCA, resulting in a 6% incidence in lesion frequency; this was not significantly different from controls. KC juveniles exposed to 400 μg/L BaP exhibited a significantly greater lesion frequency than similarly exposed ER juveniles (p = 0.018). No hepatocellular adenomas or carcinomas were found in the ER juveniles that we examined.

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