Altered CYP1A expression in Fundulus heteroclitus adults and larvae: a sign of pollutant resistance?

Elskus, Adria A.; Monosson, Emily; McElroy, Anne E.; Stegeman, John J.; Woltering, D.

doi:10.1016/s0166-445x(98)00102-7

Cited by 100 publications

(72 citation statements)

References 38 publications

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“…Control and TCDF-treated animals from both sites were found to express similar moderate levels of CYP lAl in these cells. This pattern of expression has also been detected by other groups, in adult fish Van Veld et a!., 1997 and in larvae Cantrell et a!., 1998;Elskus et al, 1999. We also examined the response of two phase II enzymes, GST and UGT. Some members of the GST and UGT gene families are part ofthe mammalian AhR gene battery Nebert et al, 1993.…”

Section: Udp Glucuronosvl Transferase Ugt Activity: the Protocol Descsupporting

confidence: 76%

Characterization of resistance to halogenated aromatic hydrocarbons in a population of Fundulus heteroclitus from a marine superfund site

Bello¹

1999

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New Bedford Harbor NBH, MA, is contaminated with halogenated aromatic hydrocarbons HAH including some potent aryl hydrocarbon receptor AhR agonists. To determine ifFundulus heterocitus from NBH have developed resistance to HAll, we examined the inducibility of cytochrome P4501A1 CYP1A1 in fish from NBH and Scorton Creek SC, reference site. Despite higher PCB concentrations in NBH than in SC fish --1 500-fold -CYP1A1 expression, in most tissues, was not higher in NBH fish than in SC fish. Glutathione S-transferase GST and UDP-glucuronosyltransferase UGT activities were higher in NBH fish than in SC fish, but only when fish were collected during different seasons. GST activity was higher in the intestines ofNBH fish than in any other tissue.2,3,7,8-Tetrachlorodibenzoftiran TCDF induced CYP1A1 expression, in all tissues examined, in SC fish. In contrast, NBH fish showed little CYP1A1 induction by any measure, in any tissue. Hepatic GST activity was induced only in male NBH fish. Hepatic UGT activity showed no relationship to treatment in fish from either site.2,3,7,8-Tetrachlorodibenzo-p-dioxin TCDD and J3-naphthoflavone BNF induced CYP1A1 activity to the same level in primary cultures ofhepatocytes from either SC orNBH fish. However, hepatocytes from NBH fish were 14-fold less sensitive to TCDD and 3-fold less sensitive to BNF than hepatocytes from SC fish.To examine the heritability ofresistance, NBH and SC F1 fish were treated with 3H-TCDD or BNF. 3H-TCDD induced CYP1A1 expression only in SC F1 fish. BNF induced CYP1A1 expression in both SC and NBH F1 fish. There was no significant difference in hepatic 3H-TCDD concentrations between SC and NBH F1 fish.Hepatic AhR content, as measured by photoaffinity labeling with '25I-N3Br2DD, was lower in NBH fish than in SC fish and lower in males than in females. After 90 days in captivity, the sex difference persisted, but the site difference did not. TCDF induced hepatic AIIR content in NBH F1 fish.These results indicate that NBH Fundulus have developed a pre-translational, systemic, heritable resistance to HAHs. These findings suggest that an alteration in the AIIR pathway is responsible for this resistance; this is the subject ofcontinuing research. Next, I owe more than I can say to my thesis advisor and friend Mark Hahn. He was always available whenever I needed to consult on ideas, was endlessly tolerant of the bizarre hours I kept, and fostered a truly enjoyable work environment.Bruce Woodin was an ever accommodating and delightful person to work with. I want to thank him for all ofhis help with dissections, his enlightening field trips, and for generally making my time here that much more enjoyable. I thank Diana Franks for her work with the primary culturing of the Fundulus hepatocytes, for her help with fish care and for generally helping to make my life a little easier. Diane Nacci, Ken Rocha, and the EPA laboratory in Narragansette for kindly providing fish. Diane also for her help during the planning stages ofthis work and her willingness to exchange r...

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Section: Udp Glucuronosvl Transferase Ugt Activity: the Protocol Descsupporting

confidence: 76%

Characterization of resistance to halogenated aromatic hydrocarbons in a population of Fundulus heteroclitus from a marine superfund site

Bello¹

1999

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“…However, a range of LD 50 values for TCDD can exist within a species, dependent on exposure conditions or strain of fish Wright et al, 1996). It is also interesting to note that certain populations of Fundulus can develop resistance to TCDD in the environment (Prince and Cooper, 1995;Elskus et al, 1999;Hahn, 1998). Thus, both physiological and genetic factors can influence the relative sensitivity of a particular strain (or population) of fish within a species.…”

Section: Discussionmentioning

confidence: 99%

“…Fundulus larvae and adults from other populations have a low basal level of CYP1A expression in proximal tubules of the kidney even in the control fish (Elskus et al, 1999;Bello et al, 2000). CYP1A is only active at low basal levels during the embryonic stages (Binder and Stegeman, 1984) and may not be detected using immunohistochemical techniques.…”

Section: Discussionmentioning

confidence: 99%

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptotic cell death and cytochrome P4501A expression in developing Fundulus heteroclitus embryos

et al. 2001

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“…Specifically, all of these populations exhibit a marked reduction in CYP1A inducibility in response to a variety of AhR agonists (Prince and Cooper, 1995a;Elskus et al, 1999;Nacci et al, 1999;Bello et al, 2001;Arzuaga and Elskus, 2002;Meyer et al, 2002. To more fully understand alterations to the AhR pathway, CYP1A was chosen as the target for morpholino gene knockdown in killifish from a reference site.…”

Section: Introductionmentioning

confidence: 99%

Development of the morpholino gene knockdown technique in Fundulus heteroclitus: A tool for studying molecular mechanisms in an established environmental model

et al. 2008

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a b s t r a c t A significant challenge in environmental toxicology is that many genetic and genomic tools available in laboratory models are not developed for commonly used environmental models. The Atlantic killifish (Fundulus heteroclitus) is one of the most studied teleost environmental models, yet few genetic or genomic tools have been developed for use in this species. The advancement of genetic and evolutionary toxicology will require that many of the tools developed in laboratory models be transferred into species more applicable to environmental toxicology. Antisense morpholino oligonucleotide (MO) gene knockdown technology has been widely utilized to study development in zebrafish and has been proven to be a powerful tool in toxicological investigations through direct manipulation of molecular pathways. To expand the utility of killifish as an environmental model, MO gene knockdown technology was adapted for use in Fundulus. Morpholino microinjection methods were altered to overcome the significant differences between these two species. Morpholino efficacy and functional duration were evaluated with molecular and phenotypic methods. A cytochrome P450-1A (CYP1A) MO was used to confirm effectiveness of the methodology. For CYP1A MO-injected embryos, a 70% reduction in CYP1A activity, a 86% reduction in total CYP1A protein, a significant increase in ␤-naphthoflavone-induced teratogenicity, and estimates of functional duration (50% reduction in activity 10 dpf, and 86% reduction in total protein 12 dpf) conclusively demonstrated that MO technologies can be used effectively in killifish and will likely be just as informative as they have been in zebrafish.

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Altered CYP1A expression in Fundulus heteroclitus adults and larvae: a sign of pollutant resistance?

Cited by 100 publications

References 38 publications

Characterization of resistance to halogenated aromatic hydrocarbons in a population of Fundulus heteroclitus from a marine superfund site

Characterization of resistance to halogenated aromatic hydrocarbons in a population of Fundulus heteroclitus from a marine superfund site

2,3,7,8-Tetrachlorodibenzo-p-dioxin induces apoptotic cell death and cytochrome P4501A expression in developing Fundulus heteroclitus embryos

Development of the morpholino gene knockdown technique in Fundulus heteroclitus: A tool for studying molecular mechanisms in an established environmental model

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