Varying degrees of susceptibility of inbred strains of rats to N-2-fluorenyldiacetamide hepatic carcinogenesis*1

Reuber, Melvin D.

doi:10.1016/0041-008x(76)90214-3

Cited by 5 publications

(2 citation statements)

References 14 publications

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“…The ability to produce toxicity was related to hepatic N-hydroxy-2-aminofluorene sulfotransferase activity with greater activity in female F-344 and Wistar rats and markedly less in SD liver, indicating that a metabolite may be responsible for toxicity. In a subsequent study, Reuber (70) found that male F-344 and ACI rats treated with N-2fluorenyldiacetamide developed cirrhosis and carcinoma of the liver, whereas Marshall strain rats were resistant. As in the case of chemical-induced renal and intestinal damage, the male was markedly more susceptible to acetylaminofluorene-induced hepatotoxicity.…”

Section: Livermentioning

confidence: 96%

Review Article: Strain as a Determinant Factor in the Differential Responsiveness of Rats to Chemicals

Kacew

Ruben

McConnell³

1995

Toxicol Pathol

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The beneficial effects derived from the use of chemicals in agriculture, energy production, transportation, pharmaceuticals, and other products that improve the quality of life are clearly established. However, continued exposure to these chemicals is only advantageous in conditions where the benefit far outweighs toxic manifestations. By law, determination of risk of toxicity necessitates the use of laboratory animals to establish whether chemical exposure is safe for humans. To simulate the human condition, it is incumbent upon investigators to choose a species in which pharmacokinetic and toxicokinetic principles are established and resemble those of humans. Some of the advantages to the use of rat in chemical toxicity testing include (a) similarities in metabolism, anatomy, and physiological parameters to humans; (b) the short life span, especially for carcinogenesis study; (c) the availability, ease of breeding, and maintenance at a relatively low cost; and (d) the existence of a large database to enable comparison of present to reported literature findings. However, the choice of rat can be complicated by several factors such as sex, age, and nutrition, but especially strain, where currently there are over 200 different strains of rat known to exist. The aim of this review is to demonstrate that there are differences in the responsiveness of rat strains to chemicals and that the susceptibility observed is dependent on the tissue examined. It is evident that the genotype differs among strains, and this may be responsible for differences in sensitivities to chemicals. Awareness of strain as a factor in susceptibility to toxicant action needs to be taken into account in interpretation of relevance of risk of toxicity for humans.

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Section: Livermentioning

confidence: 96%

Review Article: Strain as a Determinant Factor in the Differential Responsiveness of Rats to Chemicals

Kacew

Ruben

McConnell³

1995

Toxicol Pathol

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“…For many rodent strains this has resulted in progressively larger, more obese animals with higher spontaneous tumor rates and reduced lifespans. This genetic drift has compromised assay sensitivity and the usefulness of some rodent strains in carcinogenicity testing and has diminished the value of the historical tumor record for these strains (65)(66)(67)(68)(69) (70)(71)(72)(73)(74)(75)(76)(77)(78). Many of these differences may be due to species-and strain-related (genetic) differences in metabolism and pharmacokinetics.…”

Section: Validation Of Carcinogenicity Bioassaysmentioning

confidence: 99%

In Vivo Transgenic Bioassays and Assessment of the Carcinogenic Potential of Pharmaceuticals

Contrera¹,

DeGeorge²

1998

Environmental Health Perspectives

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There is general agreement in the scientific community on the need to improve carcinogenicity testing and the assessment of human carcinogenic risk and to incorporate more information on mechanisms and modes of action into the risk assessment process. Advances in molecular biology have identified a growing number of genes such as protooncogenes and tumorsuppressor genes that are highly conserved across species and are assocjated with a wide variety of human and animal cancers. In vivo transgenic rodent models incorporating such mechanisms are used to identify mechanisms involved in tumor formation and as selective tests for carcinogens. Transgenic methods can be considered an extension of genetic manipulation by selective breeding, which long has been employed in science and agriculture. The use of two rodent species in carcinogenicity testing is especially important for identifying transspecies carcinogens. The capacity of a substance to induce neoplasia across species suggests that the mechanism(s) involved in the induction of the neoplasia are conserved and therefore may have significance for humans. Based on available information there is sufficient experience with some in vivo transgenic rodent carcinogenicity models to support their application as complementary second species studies in conjunction with a single 2-year rodent carcinogenicity study. The optional substitution of a second 2-year rodent carcinogenicity study with an alternative study such as an in vivo transgenic carcinogenicity study is part of the International Conference on Harmonization guidance Si B: Testing for Carcinogenicity of Pharmaceuticals. This guidance is intended to be flexible enough to accommodate a wide range of possible carcinogenicity assessment models currently under consideration or models that may be developed in the future. The use of an in vivo transgenic mouse model in place of a second 2-year mouse study will improve the assessment of carcinogenic risk by contributing insights into the mechanisms of tumorigenesis and potential human relevance not available from a standard 2-year bioassay. It is envisioned that this will stimulate the further development of more efficient and relevant methods for identifying and assessing potential human carcinogenic risk, which will benefit public health.Environ Health Perspect 106(Suppl 1): 71-80 (1998). http.//ehpnet1.niehs.nih.gov/ docs/1998/Suppl-1/71-80contrera/abstract.html

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Effect of Genetic Susceptibility on Tumor Induction

Drinkwater¹

1995

Chemical Induction of Cancer

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Varying degrees of susceptibility of inbred strains of rats to N-2-fluorenyldiacetamide hepatic carcinogenesis*1

Cited by 5 publications

References 14 publications

Review Article: Strain as a Determinant Factor in the Differential Responsiveness of Rats to Chemicals

Review Article: Strain as a Determinant Factor in the Differential Responsiveness of Rats to Chemicals

In Vivo Transgenic Bioassays and Assessment of the Carcinogenic Potential of Pharmaceuticals

Effect of Genetic Susceptibility on Tumor Induction

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