Evaluation of the E mu-pim-1 transgenic mouse model for short-term carcinogenicity testing

C. F. van Kreijl, C. W. V. van Oordt, E. D. Kroese, Ilona Kryspin Sørensen, M. L. Breuer, R. D. Storer

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The value of the chronic rodent carcinogenicity assay in adequately predicting cancer risk in humans has become a matter of debate over the past few years. Therefore, more rapid and accurate alternative tests are urgently needed. Transgenic mouse models, those harboring genetic changes that are relevant to the multistage cancer process, may provide such alternative tests. Transgenic E mu-pim-1 mice, developed by Berns and coworkers in 1989, contain the pim-1 oncogene, which is expressed at elevated levels in their lymphoid compartments. As a result, these mice are predisposed to the development of T-cell lymphomas. Because of the low incidence of spontaneous tumors and the increased sensitivity to N-ethyl-N-nitrosourea-induced carcinogenesis, E mu-pim-1 mice were suggested to be one of the first potential and attractive candidates to be used in short-term carcinogenicity testing. In the present article, the results from 2 recent short-term assays (with mitomycin C and x-rays) are briefly presented, together with a review of all 11 performed bioassays and their corresponding histopathologic and molecular data. The overall results allow the first evaluation of the E mu-pim-1 mouse model with regard to its usefulness in short-term carcinogenicity testing. It has been shown that the model is primarily suitable as a sensitive short-term assay for genotoxic carcinogens that not only induce (at least) gene mutations and/or large deletions and rearrangements but that also sufficiently target the lymphoid system. However, the E mu-pim-1 mice lack sufficient sensitivity to justify their routine use in short-term carcinogenicity testing in general.
Original languageEnglish
JournalToxicologic Pathology
Volume26
Issue number6
Pages (from-to)750-756
ISSN0192-6233
Publication statusPublished - 1998

Cite this

van Kreijl, C. F., van Oordt, C. W. V., Kroese, E. D., Sørensen, I. K., Breuer, M. L., & Storer, R. D. (1998). Evaluation of the E mu-pim-1 transgenic mouse model for short-term carcinogenicity testing. Toxicologic Pathology, 26(6), 750-756.
van Kreijl, C. F. ; van Oordt, C. W. V. ; Kroese, E. D. ; Sørensen, Ilona Kryspin ; Breuer, M. L. ; Storer, R. D. / Evaluation of the E mu-pim-1 transgenic mouse model for short-term carcinogenicity testing. In: Toxicologic Pathology. 1998 ; Vol. 26, No. 6. pp. 750-756.
@article{fee4149592c0490ba1e4e90a626c5105,
title = "Evaluation of the E mu-pim-1 transgenic mouse model for short-term carcinogenicity testing",
abstract = "The value of the chronic rodent carcinogenicity assay in adequately predicting cancer risk in humans has become a matter of debate over the past few years. Therefore, more rapid and accurate alternative tests are urgently needed. Transgenic mouse models, those harboring genetic changes that are relevant to the multistage cancer process, may provide such alternative tests. Transgenic E mu-pim-1 mice, developed by Berns and coworkers in 1989, contain the pim-1 oncogene, which is expressed at elevated levels in their lymphoid compartments. As a result, these mice are predisposed to the development of T-cell lymphomas. Because of the low incidence of spontaneous tumors and the increased sensitivity to N-ethyl-N-nitrosourea-induced carcinogenesis, E mu-pim-1 mice were suggested to be one of the first potential and attractive candidates to be used in short-term carcinogenicity testing. In the present article, the results from 2 recent short-term assays (with mitomycin C and x-rays) are briefly presented, together with a review of all 11 performed bioassays and their corresponding histopathologic and molecular data. The overall results allow the first evaluation of the E mu-pim-1 mouse model with regard to its usefulness in short-term carcinogenicity testing. It has been shown that the model is primarily suitable as a sensitive short-term assay for genotoxic carcinogens that not only induce (at least) gene mutations and/or large deletions and rearrangements but that also sufficiently target the lymphoid system. However, the E mu-pim-1 mice lack sufficient sensitivity to justify their routine use in short-term carcinogenicity testing in general.",
author = "{van Kreijl}, {C. F.} and {van Oordt}, {C. W. V.} and Kroese, {E. D.} and S{\o}rensen, {Ilona Kryspin} and Breuer, {M. L.} and Storer, {R. D.}",
year = "1998",
language = "English",
volume = "26",
pages = "750--756",
journal = "Toxicologic Pathology",
issn = "0192-6233",
publisher = "SAGE Publications",
number = "6",

}

van Kreijl, CF, van Oordt, CWV, Kroese, ED, Sørensen, IK, Breuer, ML & Storer, RD 1998, 'Evaluation of the E mu-pim-1 transgenic mouse model for short-term carcinogenicity testing', Toxicologic Pathology, vol. 26, no. 6, pp. 750-756.

Evaluation of the E mu-pim-1 transgenic mouse model for short-term carcinogenicity testing. / van Kreijl, C. F.; van Oordt, C. W. V.; Kroese, E. D.; Sørensen, Ilona Kryspin; Breuer, M. L.; Storer, R. D.

In: Toxicologic Pathology, Vol. 26, No. 6, 1998, p. 750-756.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Evaluation of the E mu-pim-1 transgenic mouse model for short-term carcinogenicity testing

AU - van Kreijl, C. F.

AU - van Oordt, C. W. V.

AU - Kroese, E. D.

AU - Sørensen, Ilona Kryspin

AU - Breuer, M. L.

AU - Storer, R. D.

PY - 1998

Y1 - 1998

N2 - The value of the chronic rodent carcinogenicity assay in adequately predicting cancer risk in humans has become a matter of debate over the past few years. Therefore, more rapid and accurate alternative tests are urgently needed. Transgenic mouse models, those harboring genetic changes that are relevant to the multistage cancer process, may provide such alternative tests. Transgenic E mu-pim-1 mice, developed by Berns and coworkers in 1989, contain the pim-1 oncogene, which is expressed at elevated levels in their lymphoid compartments. As a result, these mice are predisposed to the development of T-cell lymphomas. Because of the low incidence of spontaneous tumors and the increased sensitivity to N-ethyl-N-nitrosourea-induced carcinogenesis, E mu-pim-1 mice were suggested to be one of the first potential and attractive candidates to be used in short-term carcinogenicity testing. In the present article, the results from 2 recent short-term assays (with mitomycin C and x-rays) are briefly presented, together with a review of all 11 performed bioassays and their corresponding histopathologic and molecular data. The overall results allow the first evaluation of the E mu-pim-1 mouse model with regard to its usefulness in short-term carcinogenicity testing. It has been shown that the model is primarily suitable as a sensitive short-term assay for genotoxic carcinogens that not only induce (at least) gene mutations and/or large deletions and rearrangements but that also sufficiently target the lymphoid system. However, the E mu-pim-1 mice lack sufficient sensitivity to justify their routine use in short-term carcinogenicity testing in general.

AB - The value of the chronic rodent carcinogenicity assay in adequately predicting cancer risk in humans has become a matter of debate over the past few years. Therefore, more rapid and accurate alternative tests are urgently needed. Transgenic mouse models, those harboring genetic changes that are relevant to the multistage cancer process, may provide such alternative tests. Transgenic E mu-pim-1 mice, developed by Berns and coworkers in 1989, contain the pim-1 oncogene, which is expressed at elevated levels in their lymphoid compartments. As a result, these mice are predisposed to the development of T-cell lymphomas. Because of the low incidence of spontaneous tumors and the increased sensitivity to N-ethyl-N-nitrosourea-induced carcinogenesis, E mu-pim-1 mice were suggested to be one of the first potential and attractive candidates to be used in short-term carcinogenicity testing. In the present article, the results from 2 recent short-term assays (with mitomycin C and x-rays) are briefly presented, together with a review of all 11 performed bioassays and their corresponding histopathologic and molecular data. The overall results allow the first evaluation of the E mu-pim-1 mouse model with regard to its usefulness in short-term carcinogenicity testing. It has been shown that the model is primarily suitable as a sensitive short-term assay for genotoxic carcinogens that not only induce (at least) gene mutations and/or large deletions and rearrangements but that also sufficiently target the lymphoid system. However, the E mu-pim-1 mice lack sufficient sensitivity to justify their routine use in short-term carcinogenicity testing in general.

M3 - Journal article

VL - 26

SP - 750

EP - 756

JO - Toxicologic Pathology

JF - Toxicologic Pathology

SN - 0192-6233

IS - 6

ER -

van Kreijl CF, van Oordt CWV, Kroese ED, Sørensen IK, Breuer ML, Storer RD. Evaluation of the E mu-pim-1 transgenic mouse model for short-term carcinogenicity testing. Toxicologic Pathology. 1998;26(6):750-756.