Critical Effective Methods to Detect Genotoxic Carcinogens and Neoplasm-Promoting Agents

Weisburger, John H.; Williams, Gary M.

doi:10.2307/3430855

Cited by 19 publications

(6 citation statements)

References 15 publications

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“…Be that as it may, the relatively high prevalence of foci of cellular alteration in the liver of dab from Stn 3, coupled with prominent mitotic activity and little evidence of apoptosis, collectively suggests a toxic effect with at least a reduction in those homeostatic mechanisms that regulate normal liver growth. Whether the environmental triggers are genotoxic or epigenetic carcinogens, promoters or enhancing factors, etc., remains to be established (see Weisburger & Williams 1991). In parallel studies to this one, Chipman et al (1992) found no evidence of genotoxic liver damage in dab sampled along the transect.…”

Section: Stnmentioning

confidence: 91%

Toxicological pathology of dab Limanda limanda along pollution gradients in the southern North Sea

Simpson¹,

Hutchinson²

1992

Mar. Ecol. Prog. Ser.

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During the Bremerhaven Workshop non-overtly diseased female dab Limanda lirnanda, 17 to 27 cm in length, were sampled for detailed histopathology along a 200 km transect (Stns 3, 5, 6, 7, 8 & 9) extending out from the Elbe estuary region (Stn 3) to the northwestern region of the Dogger Bank (Stn 9) in the southern North Sea. During the period March 12 to 30, 1990, approximately 20 fish were examined from each of the above stations Histopathological changes seen that were considered to be consistent with adverse exposure to xenobiotic compounds were confined to the heart, liver and kidney. In the heart, the prevalence of myocardial vacuolation, suggestive of fatty change, was significantly higher (p < 0.05) in fish from Stn 3 compared to fish from all other stations. In the llver, the most important lesions seen were well-developed foci of cellular alteration, high mitotlc activity and high neutral lipid accumulation in livers of dab sampled from the most inshore station (Stn 3) compared to the reference station (Stn 7). Foci of cellular alteration and high neutral lipid accumulation were significantly greater ( p < 0.05) at Stn 3 compared to Stn 7. In the kidney, the prevalance of proteinaceous/cellular debris in Bowman's space of renal glomeruli was significantly greater ( p < 0.01) in fish from Stn 3 compared to fish from Stn 7 The high prevalence of foci of cellular alteration and high neutral lipid accumulation In hepatocytes in the liver of dab are consistent with the effects of adverse exposure to toxic xenobiotics. The other non-infectious changes seen in the liver, as well as those seen In the heart and kidney, are also consistent with xenobiotic exposure but other possible explanations are considered. The value of using detailed histopathology on small numbers of dab which appear grossly normal is clearly demonstrated.

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Section: Stnmentioning

confidence: 91%

Toxicological pathology of dab Limanda limanda along pollution gradients in the southern North Sea

Simpson¹,

Hutchinson²

1992

Mar. Ecol. Prog. Ser.

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“…The most commonly reported are gamma-gluta-myl transpeptidase (GGT), glutathione-S-transferase (GST), the cytochrome P-450s, iron exclusion, and oncogene/tumor suppressor gene expression. A large body of research also exists on DNA-carcinogen adducts in fish, and readers are referred to other reference sources (53,187,209).…”

Section: Molecular Markersmentioning

confidence: 99%

Review Article: Experimental Chemical Carcinogenesis in Fish

Bunton

1996

Toxicol Pathol

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Dr. Bunton's primary research interest is on mechanisms of toxicity and carcinogenesis in fish related to environmental contamination and on the development of alternative models.Experimental carcinogenesis using fish species as alternative models is a dynamic field of research. The 1940's expansion of synthetic chemical producing industries coincided with a number of pollution-associated fish neoplasia epizootics, with polycyclic aromatic hydrocarbons as significant components of contaminated sediment in several cases. Epizootics of primarily liver and skin neoplasia in benthic species near coastal urban or industrial areas indicated the sensitivity of fish species to known mammalian carcinogens. Stressing a mechanistic approach, investigators have used data compiled from epizootics as the backbone of current research efforts to define carcinogenesis in fish species. With liver as the focus, patterns of neoplastic development similar to those seen in rodent bioassays have been induced in various fish species by genotoxic carcinogens. Similarities between fish and rodent models include chemical and species-specific responses to exposure and the development of predictable preneoplastic and neoplastic lesions. The expression of molecular molecules related to carcinogenesis is currently under investigation, which includes alterations in certain proteins, enzyme activity, and oncogene/tumor suppressor gene function. The potential for the application of research findings to both human and environmental health issues makes fish species attractive and valuable alternative models in carcinogenesis and toxicity research.Keywords. Medaka; methylazoxymethanol (MAM); molecular markers; N-methyl-N'-nitro-N-nitrosoguanidine (MNNG); Neoplasia; polycyclic aromatic hydrocarbons (PAH); rainbow trout INTRODUCTION Armed with data from fish neoplasia epizootics related to environmental synthetic chemical contamination, research has moved from the morphologic assessment of neoplasms to the identification of molecular mechanisms of neoplastic development and progression. The value of these studies can be argued along 2 lines that are often, but should not be, separated. One is for application to human health issues for which there is a chronic demand, and the other is the inherent value of monitoring the health of the environment, which includes all of the creatures therein. Unfortunately, it is the latter argument that most often has to be vigorously defended, although minimal reflection will reveal that we, too, are members of this population.The present review discusses experimental fish carcinogenesis by first presenting data from neoplasia epizootics that helped to form the framework of our current 604 research efforts. The effects of known direct and indirect carcinogens on various fish species from laboratory studies are then described to illustrate species similarities and differences in tissue response. The latter portion of the paper concentrates on chemical hepatocarcinogenesis and reviews the histologic and molecular marke...

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“…It is also known that there are some disadvantages of the Ames test system. Firstly, it is a short term test which can give false results; both positive and negative false results (Weisburger & Williams, 1991). Secondly, Salmonella is a prokaryotic organism.…”

Section: Discussionmentioning

confidence: 99%

Isolation of some luteolin derivatives from Mentha longifolia (L.) Hudson subsp. longifolia and determination of their genotoxic potencies

et al. 2012

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Critical Effective Methods to Detect Genotoxic Carcinogens and Neoplasm-Promoting Agents

Cited by 19 publications

References 15 publications

Toxicological pathology of dab Limanda limanda along pollution gradients in the southern North Sea

Toxicological pathology of dab Limanda limanda along pollution gradients in the southern North Sea

Review Article: Experimental Chemical Carcinogenesis in Fish

Isolation of some luteolin derivatives from Mentha longifolia (L.) Hudson subsp. longifolia and determination of their genotoxic potencies

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