Genotoxicity Studies
The ability or potential of the test item to induce genetic mutations is evaluated, both in vitro and in vivo studies, to arrive at this decision.
Ames Test: Here strains of Salmonella typhimurium and Escharacia coli, which require histidine and tryphtophan, respectively, for growth are used. The principle being that if the test drug causes a mutation that reverses the mutation already present in the organisms, the revertant strains will be able to grow in media devoid of the amino acid essential for their growth (unlike the original revertant strains) and show an increase in the number of revertant colonies compared to the control group.
Chromosome Aberration Assay: This assay is used to assess the potential of a test drug to induce damage, structural (clastogenicity) and /or numerical (polyploidy or aneuploidy), to chromosomes. This assay may be conducted in Chinese Hamster Ovary (CHO) cells or human peripheral blood lymphocytes (HPBL). Most chromosome aberrations are lethal to the cells, however, small deletions, rearrangements or translocations and variations in numbers are not lethal and these are detected by the in vitro Chromosome Aberration Assay.
Micronucleus Test: This test may be conducted in mice or rats. Many prefer to conduct this study in rats since the repeat dose studies were conducted in rats and a fairly large body of data exists on how the rat handles the test drug, both by way of exposures and toxicities. After a dose-range-finding study conducted to select doses for the main study, the animals are dosed for two consecutive days and then sacrificed. Bone marrow smears are prepared and evaluated to determine cytotoxicity and genotoxic potential of the test drug.
