Chemical carcinogenesis studies in nonhuman primates

Takayama, Seiji; Thorgeirsson, Unnur P.; Adamson, Richard H.

doi:10.2183/pjab.84.176

Cited by 42 publications

(20 citation statements)

References 29 publications

(50 reference statements)

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“…Ennever and Lave (2003) also have discussed the chemical combination of aspirin/phenacetin/ caffeine, which is classified as a human carcinogen but tested negative in both rodent species (Ennever and Lave, 2003 In the absence of human data, it might be considered reasonable to use data from tests in nonhuman primates for comparative purposes. Cancer bioassays in nonhuman primates were carried out on 37 compounds within 34 years (Takayama et al, 2008); the results were "... Inconclusive in many cases," but carcinogenicity was shown unequivocally for four of them.…”

Section: Scientific Relevancementioning

confidence: 99%

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Basketter

Clewell

Kimber

et al. 2012

ALTEX

202

165

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Section: Scientific Relevancementioning

confidence: 99%

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Basketter

Clewell

Kimber

et al. 2012

ALTEX

202

165

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“…For example, over a 34-year period the US National Cancer Institute carried out an investigation of 37 chemicals in long-term studies in NHP. 171,172 Two of the immunosuppressant drugs of interest cyclophosphamide and azathioprine were included in this program. The results from the cyclophosphamide study were considered to be inconclusive.…”

Section: View To the Futurementioning

confidence: 99%

Critical Review of Preclinical Approaches to Evaluate the Potential of Immunosuppressive Drugs to Influence Human Neoplasia

Bugelski¹,

Volk²,

Walker³

et al. 2010

Int J Toxicol

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Many immunosuppressive drugs are associated with an increased risk of B-cell lymphoma, squamous cell carcinoma, and Kaposi sarcoma. Thirteen immunosuppressive drugs have been tested in 2-year carcinogenicity studies (abatacept; azathioprine; busulfan; cyclophosphamide; cyclosporine; dexamethasone; everolimus; leflunomide; methotrexate; mycophenolate mofetil; prednisone; sirolimus; and tacrolimus) and in additional models including neonatal and genetically modified mice; chemical, viral, ultraviolet, and ionizing radiation co-carcinogenesis, and in models with transplanted tumor cells. The purpose of this review is to outline the mechanisms by which immunosuppressive drugs can influence neoplasia, to summarize the available preclinical data on the 13 drugs, and to critically review the performance of the models. A combination of primary tumor and metastasis assays conducted with transplanted cells may provide the highest value for hazard identification and can be applied on a case-by-case basis. However, for both small molecules and therapeutic proteins, determining the relative risk to patients from preclinical data remains problematic. Classifying immunosuppressive drugs based on their mechanism of action and hazard identification from preclinical studies and a prospective pharmacovigilance program to monitor carcinogenic risk may be a feasible way to manage patient safety during the clinical development program and postmarketing.

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“…In the 1970s, HCAs a mutagenic class of compound were detected in cooked meat (Sugimura et al 1997). From the Ames test, the researchers have identified numerous substances which display enormously high mutagenic potency; 100 to 100000 times greater than N-nitroso compounds and polycyclic aromatic hydrocarbons (Nagao et al 1977;Takayama et al 2008;De Stefani et al 1997).…”

Section: Introductionmentioning

confidence: 99%

Influence of food condiments on the formation of carcinogenic heterocyclic amines in cooked chicken and determination by LC-MS/MS

Khan

2015

Food Additives & Contaminants: Part A

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Heterocyclic amines (HCAs) are known to be suspected human carcinogens produced by high-temperature cooking of protein-rich foods such as meat and fish. In the present study, the influence of numerous food condiments on the formation of HCAs in cooked chicken was investigated. Chicken samples were subjected to pan-frying under controlled temperature. The levels of HCAs DMIP, MeIQx, 4,8-DiMeIQx, PhIP, harman and norharman were found to be between 0.93 and 27.52 ng g(-1), whereas IQ, MeIQ, AαC, MeAαC, Trp-P-1 and Trp-P-2 were found either below the limit of quantification or not detected in the control sample. Nevertheless, for samples cooked using food condiments, the amounts of HCAs (DMIP, MeIQx, 4,8-DiMeIQx and PhIP) were between 0.14 and 19.57 ng g(-1); harman and norharman were detected at higher concentrations up to 17.77 ng g(-1) while IQ and MeIQ were at levels below the limit of quantification; and AαC, MeAαC, Trp-P-1 and Trp-P-2 were not detected in any of the samples. The outcomes revealed that the formation of HCAs (except harman and norharman) diminished after the addition of food condiments. Edible oil contributed to the highest levels of HCA formation, followed by garlic, paprika, pepper and tomato.

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Chemical carcinogenesis studies in nonhuman primates

Cited by 42 publications

References 29 publications

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

A roadmap for the development of alternative (non-animal) methods for systemic toxicity testing

Critical Review of Preclinical Approaches to Evaluate the Potential of Immunosuppressive Drugs to Influence Human Neoplasia

Influence of food condiments on the formation of carcinogenic heterocyclic amines in cooked chicken and determination by LC-MS/MS

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