The Nutritional Biochemistry of Chromium(III) - Survival-training.info

Evaluation of chromium(III) genotoxicity with cell culture and in vitro assays 211is metabolized to Cr 3+ in the body, and Cr 3+ may be one of the ultimate speciesthat interacts with DNA in Cr 6+ -induced cancers [31, 32]. Second, the chemistry andbioavailability of Cr 3+ is altered by its coordinating ligands. For example, the Cr 3+ ionin CrPic is more bioavailable than dietary Cr 3+ ,Cr 3+ can accumulate in humans [33],and the coordination of Cr 3+ by aromatic ligands like picolinate can alter the chemistryof Cr 3+ making it more toxic than other forms of Cr 3+ [34].Carcinogenicity of a chemical is ultimately defined through human epidemiologystudies or animal experiments. However, these studies are relatively costly and timeconsuming. Therefore, several cell culture and in vitro assays have been developed asscreening tools and are accepted by regulatory agencies as a first step in predictingmutagenicity or carcinogenicity of chemicals or drugs.JUSTIFICATION FOR USING CELL CULTURE AND IN VITRO ASSAYSThe purpose of short-term in vitro genotoxicity assays is to predict if a chemical mayhave a potential to cause cancer and to offer information regarding chemical mechanismsof DNA damage. These tests do not “prove” that something causes cancer, nor is thereone single test that provides an unequivocal ruling that a given substance is a carcinogen.A carcinogen is generally accepted as an agent that induces neoplasms in humans oranimals, increases the incidence of tumors, or speeds up the time for tumor development.Cancer is currently the second leading cause of death in the United States after heartdisease. Established human carcinogens include physical agents such as UV light [35],x-radiation, and gamma radiation [36], infectious agents such as hepatitis B and Cviruses [37], human papilloma viruses [38], and helicobacter pylori bacterium [39], andmany chemical agents including alcohol [40], aflatoxin [41], Cr 6+ [42], and polycyclicaromatic hydrocarbons [43].The majority of carcinogens are genotoxic (damage DNA) and mutagenic (causea permanent, heritable change in the content or structure of DNA); therefore, mostshort-term assays detect DNA damage, chromosomal damage, aneuploidy (change inchromosome number), or mutations. In vitro or cell culture assays are accepted as a“first phase” of the evaluation process for predicting carcinogenicity of a chemical, andmany guidelines have been issued to direct their use.STANDARD CELL CULTURE AND IN VITRO ASSAYS AND GUIDELINESFOR THEIR USEThe protocols and guidelines for genotoxicity and mutagenicity testing have been constantlyevolving since the link between chemicals, mutagens, and carcinogens was firstdiscovered [44–48]. The history of international regulatory agency involvement and protocolstandardization has been reviewed [49]. Two of the most recent workshops devotedto international standardization of protocols were the International Workshop on Standardizationof Genotoxicity Test Procedures sponsored by the International Conferenceon Environmental Mutagens in Melbourne in 1993 [50] and the International Workshopon Genotoxicity Testing Procedures sponsored by the Environmental Mutagen Society inWashington DC in 1999 [51]. Guidelines have also been issued through the International