Background and Framework for ILSI's Collaborative Evaluation Program on Alternative Models for Carcinogenicity Assessment

Robinson, Denise E.; Macdonald, J. S.

doi:10.1080/019262301753178438

Cited by 84 publications

(59 citation statements)

References 4 publications

(1 reference statement)

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“…This mouse model was endorsed and validated by the International Life Science Institute Health and Environmental Science Institute (ILSI HESI) through an international collaborative project (Robinson and MacDonald 2001) as an alternative to the conventional 2-year carcinogenicity bioassays in mice. Under the ILSI HESI project, 26-week carcinogenicity studies in Tg.rasH2 mice were conducted for 21 compounds at different facilities in the United States, Japan, and Europe (Takaoka et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Incidence of Spontaneous Non-Neoplastic Lesions in Transgenic CBYB6F1-Tg(HRAS)2Jic Mice

et al. 2013

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Since 2003, the Tg.rasH2 model has been accepted by regulatory agencies worldwide for 26-week short-term carcinogenicity assays as an alternative to the standard 2-year assays in conventional mice. However, over the decade, the number of actual studies conducted with alternative mouse models has remained low. The primary cause for low acceptance of this model has been lack of a historical database for the incidence of spontaneous lesions. Recently, we published the historical control database on spontaneous tumors in the Tg.rasH2 mice. The purpose of this publication is to present a large database pertaining to the non-neoplastic spontaneous lesions noted in Tg.rasH2 mice from studies conducted at our facility. Lesions that are considered unique in Tg.rasH2 mice are skeletal muscle myopathy, vascular anomalies involving various organs, and mesenteric arterial thrombosis. Other notable lesions are extramedullary hematopoiesis of spleen, subacute inflammatory foci in the liver, and infiltration of histiocytes in the lungs.

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Section: Introductionmentioning

confidence: 99%

Incidence of Spontaneous Non-Neoplastic Lesions in Transgenic CBYB6F1-Tg(HRAS)2Jic Mice

et al. 2013

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“…As the standard protocol of short-term carcinogenicity test using rasH2 mice, 15 animals/sex/group were used in validation studies by ILSI/HESI (Robinson and MacDonald, 2001), and 20-25 animals/sex/group are recommended from the viewpoint of statistical power currently (Morton et al, 2002). To save the number of animals used in this study, we used the minimum number of animals based on this information.…”

Section: Experimental Designmentioning

confidence: 99%

A 26-Week Carcinogenicity Study of 2-Amino-3-Methylimidazo[4,5-f]Quinoline in rasH2 Mice

et al. 2006

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To evaluate the carcinogenic susceptibility of rasH2 mice to 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ), 7-week-old rasH2 mice and their wild-type littermates (non-Tg mice) of both the sexes were fed a diet containing 0 or 300 ppm IQ for 26 weeks. Microscopical examinations revealed that the proliferative lesions of the forestomach, including squamous cell hyperplasias, papillomas, and carcinomas, were frequently encountered in male and female rasH2 mice fed with IQ. In non-Tg mice, no significant differences in the incidence of forestomach lesions were observed between the 0 ppm and 300 ppm groups. Histopathological changes such as periportal hepatocellular hypertrophy and oval cell proliferation in the liver were more apparent in female rasH2 and non-Tg mice than in males, and the incidence of hepatocellular altered foci significantly increased in female rasH2 mice in the 300 ppm group as compared to that in the 0 ppm group. These results suggest that the carcinogenic potential of IQ can be detected in rasH2 mice by a 26-week, short-term carcinogenicity test.

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“…hesi.ilsi.org , the International Life Sciences Institute Technical Committees on alternative models for carcinogenicity assessment (Robinson and MacDonald, 2001) and on the application of genomics to mechanism-based risk assessment (Robinson et al, 2003), the COMET consortium on metabonomics (Lindon et al, 2003), and the SNP consortium (Holden, 2002) focused on development of a set of haplotype markers for identification of genetic variants that modify biological outcomes.…”

Section: Imaging: a Means Of Monitoring Molecular Biomarkers Noninvasmentioning

confidence: 99%

Biomarkers of Cancer Risk and Therapeutic Benefit: New Technologies, New Opportunities, and Some Challenges

MacGregor

2004

Toxicol Pathol

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The biotechnology revolution offers unprecedented opportunities for identification of mechanistically-based biomarkers that report and predict cancer and other pathologies. The combination of genomic technologies with a knowledge of gene sequence and sequence conservation has made available markers that facilitate the correlation of genetic variation with biological outcomes, and "-omic" technologies allow efficient biochemical characterization of functional pathways-providing new markers of the susceptibility of individuals to cancer development, and of tumor susceptibility to specific therapies. New therapeutic agents targeted to individuals with specific genetic or biochemical characteristics already exist. The powerful -omic technologies allow efficient monitoring of gene transcripts, proteins, and intermediary metabolites, making it possible to monitor a large number of key cellular pathways simultaneously. This has enabled the identification of key biomarkers and signaling molecules associated with cell growth, cell death, and cellular metabolism. These new markers are facilitating monitoring of functional disturbance, molecular and cellular damage, and damage-response. Improved imaging technologies have made it feasible to image some of these molecular events noninvasively. To meet the challenge of evaluating and developing consensus criteria for the application of these new technologies and biomarkers, consortium approaches are being increasingly undertaken to share resources and to build a common understanding among the research, industry, and regulatory communities. These developments promise more efficient pharmaceutical product development, safer and more efficacious drugs, and provide clinical practitioners with new and better biomarkers for cancer screening, patient monitoring, and choice of therapy.

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Background and Framework for ILSI's Collaborative Evaluation Program on Alternative Models for Carcinogenicity Assessment

Cited by 84 publications

References 4 publications

Incidence of Spontaneous Non-Neoplastic Lesions in Transgenic CBYB6F1-Tg(HRAS)2Jic Mice

Incidence of Spontaneous Non-Neoplastic Lesions in Transgenic CBYB6F1-Tg(HRAS)2Jic Mice

A 26-Week Carcinogenicity Study of 2-Amino-3-Methylimidazo[4,5-f]Quinoline in rasH2 Mice

Biomarkers of Cancer Risk and Therapeutic Benefit: New Technologies, New Opportunities, and Some Challenges

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