毒理学基础个人总结 Chapter 8 Mutagenesis.docxVIP

Chapter 8 MutagenesisPart 1 IntroductionMutagenicity is the ability of exogenous chemical or physical factors to cause DNA sequence changes that is transmittable during cell division.Mutagenicity is not always, but often harmful. Harmful outcomes include fertility disorders, embryonic and perinatal death, malformations, hereditary diseases, and cancers.Mutations can happen in two categories of cells—germinal cells and somatic cellsMutations of germinal cells (sperm or ovum)Potential to transmit mutations to next generationsIf mutations happen during fertilization (egg or sperm), they may cause infertility or death of fetus at a later development period (abortion).In case that the mutations are non-lethal, congenital abnormalities may result.Somatic MutationsResult in cell death or transmission of a genetic defect to other cells in the same tissue through mitotic division.A goal of toxicologists working in this area is to recognize and minimize human exposure of exogenous mutagens and prevent the increase in human “genetic load”.Part 2Categories of MutagenesisThree categories of genetic alterations:Gene mutations (point mutations)base-pair exchange, addition or deletion of one or several bases.Chromosomal aberrations (chromosomal structural abnormalities)Gross chromosomal rearrangement (deletions, duplications, inversions, and translocations)Aneuploidy and polyploidy (chromosomal numerical abnormalities)Gene MutationsBase-pair substitutionReplacement of a type of base by anotherThe smallest unit of mutationTwo kinds:Trasitions(pyrimidine to pyrimidine and purine to purine substitutions)Transversions (pyrimidine to purine and purine to pyrimidine substitutions)Frameshift MutationsAddition or deletion of a base in the DNA chain leads to misreading of the triplet codes, defined as frameshift mutations. Resulting in altered amino acid sequence of the gene product (protein) or truncation or elongation of the gene product.Acridine orange(丫啶橙）as a typical frameshift-inducin