The Tg.AC (v-Ha-ras) Transgenic Mouse: Nature of the Model

Tennant, Raymond W.; Stasiewicz, Stanley; Eastin, William C.; Mennear, John H.; Spalding, Judson W.

doi:10.1080/019262301753178474

Cited by 44 publications

(33 citation statements)

References 29 publications

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“…The International Life Sciences Institute (ILSI) sponsored a collaborative evaluation program to examine alternative models for carcinogenicity testing (Cohen et al, 2001;Robinson and MacDonald, 2001;Tennant et al, 2001). With the ILSI initiative and individual lab testing, a wide variety of chemicals have been tested on Tg.AC mice in an effort to validate the model Spalding et al, 1999Spalding et al, , 2000.…”

Section: Tgac and Chemical Carcinogenesismentioning

confidence: 99%

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

et al. 2005

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Section: Tgac and Chemical Carcinogenesismentioning

confidence: 99%

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

et al. 2005

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“…This is primarily because the Tg.AC mouse traditionally has been used in studies involving dermal application of a test chemical with subsequent enumeration of skin tumors only (Eastin et al, 2001;Tennant et al, 2001). Only one NIEHS study reported on tumor types other than skin (Tokar et al, 2010).…”

Section: Background Tumor Incidencesmentioning

confidence: 99%

In utero arsenic exposure in mice and early life susceptibility to cancer

Garry

Santamaria²,

Williams

et al. 2015

Regulatory Toxicology and Pharmacology

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In its review of the U.S. Environmental Protection Agency's toxicological review of inorganic arsenic (iAs), the National Academy of Sciences identified carcinogenic endpoints among the highest priority health effects of concern and stated the need to consider evidence that early life exposures may increase the risk of adverse health effects. Recent studies in mice suggest that in utero exposure to arsenic increases susceptibility to cancer later in life. These data are striking in light of the general lack of evidence for carcinogenicity in rodents exposed to iAs. To evaluate the transplacental carcinogenic potential of iAs, a detailed analysis of the toxicology literature evaluating the role of in utero arsenic exposure in carcinogenesis was conducted. Bladder, lung, and skin tumors, which are the tumor types most consistently reported in humans exposed to high arsenic levels, were not consistently increased in mouse studies. There was also a lack of concordance across studies for other tumor types not typically reported in humans. Therefore, we considered methodological and other critical issues that may have contributed to variable results and we suggest additional studies to address these issues. It was concluded that the available data do not provide evidence of a causal link between in utero arsenic exposure and cancer or indicate early life-stage susceptibility to arsenic-induced cancer, particularly at environmentally relevant doses.

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“…Nonetheless, specific and consistent housing and husbandry practices can effectively prevent false positive papillomas albeit at some additional cost per mouse (26). Spontaneous skin papilloma incidence in untreated or negative control groups of singlehoused mice has been reported to be less than 4% (26,35,69). The utility of the Tg.AC mouse, however, may be restricted to topical application of suspect carcinogens as oral gavage of chloroform failed to activate the v-H-ras transgene in the liver of treated mice (11).…”

Section: History Of the 2-year Rodent Bioassaymentioning

confidence: 99%

“…The Tg.AC mouse contains multiple copies of an activated form of the ras oncogene (31,69). The Tg.AC mouse is sensitive to skin papillomas and squamous cell carcinomas in response to topical application of skin tumor promoters, 355 TOXICOLOGIC PATHOLOGY presumably because the initiating mutation in Ha-ras has been provided by the v-H-ras transgene (3,64).…”

Section: History Of the 2-year Rodent Bioassaymentioning

confidence: 99%

p27 Kip1 (Cdkn1b)-Deficient Mice Are Susceptible to Chemical Carcinogenesis and May Be a Useful Model for Carcinogen Screening

Payne

Kemp

2003

Toxicol Pathol

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The two-year rodent bioassay is one of several tests that are widely used by governmental regulatory agencies as well as pharmaceutical and chemical companies to determine the carcinogenic potential of chemicals or environmental agents where human exposure is anticipated. That this assay has remained relatively unchanged for the last 25 years is a testament to the power of this approach to identify carcinogens and thus to minimize human exposure. However, there has long been controversy over the specificity and relevance of the rodent bioassay as well as its high cost in terms of time, expense, and numbers of mice. Much discussion has been generated in recent years over how to improve the 2-year rodent bioassay for more accurate and faster detection of potential human carcinogens. Here, we argue that the use of p27 Kip1 (Cdkn1b) knockout mouse for carcinogen screening may solve several shortcomings inherent in the conventional bioassay while preserving its best quality, that is, protecting public health by providing reliable in vivo information on the potential of chemicals to cause cancer.

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The Tg.AC (v-Ha-ras) Transgenic Mouse: Nature of the Model

Cited by 44 publications

References 29 publications

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

Biological, cellular, and molecular characteristics of an inducible transgenic skin tumor model: a review

In utero arsenic exposure in mice and early life susceptibility to cancer

p27 Kip1 (Cdkn1b)-Deficient Mice Are Susceptible to Chemical Carcinogenesis and May Be a Useful Model for Carcinogen Screening

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