Carcinogenicity is known as the ability of a carcinogen to cause cancer. Any chemical, biomolecule or radionuclide that is directly involved in causing cancer can be considered as a carcinogen. Generally, carcinogens increase the risk of cancer by damaging the genomic materials, altering cellular metabolic processes, or disrupting signaling pathways. Such damages normally lead to apoptosis of the damaged cell, however, if the programmed cell death pathway is damaged as well, the uncontrolled malignant division will ultimately lead to tumor formation. Carcinogens are not necessarily immediately toxic, thus their effect may not show in acute toxicity tests and require further investigation. Creative Biolabs has spent years in helping customers develop potent and safe therapeutic agents, and is capable of providing carcinogenicity investigation for drug candidates.
From carcinogenicity studies, scientists are able to get an idea of the carcinogenic properties of the tested substance, target organs of carcinogenicity, and tumor dose-response relationship. Data may also indicate their mode of action and further classify the carcinogen as genotoxic (initiate tumor development by direct interaction with DNA) or nongenotoxic (enhance carcinogenesis by affecting gene expression, signal transduction, and/or cell proliferation) carcinogens.
Carcinogenicity studies are usually animal test-based investigations that observe test animals for the development of tumors during or after exposure to different doses of a test substance for a major portion of their life span. Normally, small animals with short life spans such as rats and mice are used for such investigations. Both sexes (at least 50 animals of each sex) are included in the concurrent control group and each dose group (at least three dose levels). The test substance is given to the test animals daily according to the toxicokinetic profile. Three main routes of administration used in carcinogenicity studies are oral, dermal, and inhalation. The observation normally last for about 24 months for rodents (18 months for some specific strains of mice), though when the number of survivors in the low dose group falls below 25 percent, the study may be terminated in advance. Animals will be dissected for further analysis of tumor development. Carcinogenicity studies record animal measurements (e.g., weight, food consumption, and food efficiency), daily and detailed observations, and necropsy and histopathology. The minimum tissues that should be tested in histopathology include: all tissues from the high-dose groups; all tissues of animals dying or killed during the study; all tissues showing macroscopic abnormalities; both organs should be examined in the case of paired organs.
Some in vitro non-animal methods (cell-based assays and computational prediction models) can also be used in carcinogenicity studies. For example, cell transformation assays such as Syrian hamster embryo assay and the Balb/c 3T3 assay detect phenotypic changes (morphology, colony-forming ability, and/or growth rate) in mammalian cell cultures induced by chemicals. Carcinogenicity of the chemicals can be indicated in such tests. Structure-activity relationship models (can be quantitative and/or qualitative) such as such as TOPKAT, CASE, and DEREK are also used to predict carcinogenicity of drugs. Mutagenicity and genotoxicity assays can be used to indicate possible carcinogenic substances. Such methods significantly reduce the timeline and cost but are not sufficient to serve as full animal replacements at this time.
Creative Biolabs is capable of providing carcinogenicity investigation for drug candidates. For more detailed information, please feel free to contact us or directly sent us an inquiry.
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