The branch of genetics that studies the damage of environmental factors to genetic materials and their toxicological effects by genetic methods
Or genetic toxicology.The branch of genetics that studies the damage of environmental factors to genetic materials and their toxicological effects by genetic methods.
The genetic toxicological effects caused by environmental factors include three aspects: ① mutation formation, environmental factors induced germ cellsGene mutation（point mutation）Andchromosome aberration, resulting in offspringHereditary diseaseIncreased frequency of occurrence, ② cancer formation, induced by environmental factorssomatic cellGene mutation or induced in the background of parental genetic mutationSomatic mutation, causing the malignant transformation of somatic cells into cancer cells; ③Teratogenic effect, environmental factors affecting the developing embryonic cells interfere with the normal function of genes, thus affecting the embryocell differentiationAnd the development of organ systems, including environmental factors that induce gene mutation or chromosome aberration in parental germ cells.Mutagenicity, carcinogenesis and teratogenicity are referred to as the three effects of toxicological inheritance.In application, toxicological genetics research provides many rapid, accurate and simple methods to detect the harm of various environmental factors to the genetic structure, so as to take measures to reduce the harm of these factors to human beings.
classification
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thereforetoxicologyThe classification of is very complex and can be classified from different perspectives, but not completely consistent.
It can be divided into descriptive toxicology, mechanism toxicology andRegulatory toxicology (also known as regulatory toxicology).According to the standard disciplines, it can be divided into: forensic toxicology, clinical toxicology, management toxicology or regulatory toxicology, research toxicology, etc.From the perspective of applied toxicology, it can be divided into:Food Toxicology、Industrial ToxicologyPesticide toxicology, military toxicologyRadiotoxicology、Environmental Toxicology, ecological toxicology, etc.The research objects can be divided into:Insect Toxicology, veterinary toxicology, human toxicology and plant toxicology.The research fields can be divided into:PharmacotoxicologyEnvironmental toxicology, food toxicology, industrial toxicology, clinical toxicology, forensic toxicology, analytical toxicology, military toxicology, management toxicology, etc.From researchtarget organOr the system can be divided into:Liver Toxicology、NephrotoxicologyNeurotoxicology, reproductive toxicologyImmunotoxicology, Skintoxicology、HematotoxicologyEtc.From the perspective of mechanism research, it can be divided into: cytotoxicologyGenetic toxicology、Membrane toxicology、Biochemical toxicology、Molecular toxicology。 According to the phase or process of toxic action, it can be divided into:ToxicokineticsAnd toxic effectdynamics。
Development history
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Toxicological genetics
1927 HJ. Mahler and LJ. For Stadlerionizing radiationinduceDrosophila melanogaster, corn and barleyGene mutation。1951 and 1966 W50. Russell and BM. Katanak uses radiation andchemical substancesInduced gene mutation in mice, and believed that humanHereditary diseaseIt may also be caused by environmental factors.1968 JE. Clifford discovered that humanXeroderma pigmentosumThe patient's skin is easy to be photogenic and cancerous, and it is pointed out that this is caused by ultraviolet ray due to congenital lack of repairDNA damageAnd clearly pointed out cancer, environmental factors andDNA damage repairRelationship between.Only then did people realize that the spread of certain substances after the industrial development was a potential hazard to human genetics, and toxicology genetics came into being.1973 BN. Ames pioneered a method of using bacteriaReverse mutationAs an observation index, it is a fast and simple method to detect mutagens, and about 90% of carcinogens have mutagenic effects.Studying the relationship among mutagenicity, carcinogenesis and teratogenicity, and judging the possibility of carcinogenesis and teratogenicity of drugs by detecting mutagenicity has become an important topic in the theoretical discussion and practical application of toxicology genetics.
test method
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Detection of mutagenic, teratogenic and carcinogenic substances
Toxicological genetics
For variouschemical substancesCarcinogenesis andembryonic developmentFor the detection of teratogenic effects in the process, the early method is to feed, inject or coat the animals with the chemicals to be tested on the skin of animals, and then observe whether the animals suffer from tumors or teratogenesis due to this.This method often requires several animals and repeated tests to reach reliable conclusions, which is costly and takes a long time.The discovery that most carcinogens have mutagenic effects has prompted people to consider using simple test methods instead of animal tests.At present, bacteria or mammalian and human somatic cells cultured in vitro are generally used as test objects. The main methods are:
Detection method based on gene mutation
Ames test is the most effective method among many detection methods.It usesSalmonella typhimuriumOfhistidineThe defective strain (mutant strain that cannot grow on the medium without histidine) is the test objectchemical substancesIt can be formed on the medium without histidine after treatmentcolony of bacteria, that means it happenedReverse mutation(Figure 1).According to the number of colonies, the mutagenic ability of the substance can be estimated.Applied mammalian livermicrosomeThe enzyme system (S9) is used as the activation system to activate the substance to be tested first, which further improves the accuracy of detection by simulating the metabolism in vivo.
Chromosome based method
In addition to classicchromosome aberrationIn addition to analytical methods, the following methods have also been developed in recent years: ①micronucleusTest method tomarrow cellsorPeripheral blood lymphocytesThe number of micronuclei changes as an indicator of the test method.In addition to translocationInversionOr exchange is usually accompanied by noneCentromereThe generation of fragmentsinterval CellularcytoplasmMicronucleus, a round or oval structure, appears in the nucleus.Therefore, the number of micronuclei can be used as an indicator of chromosome aberration. ②Sister chromatidInterchange test method, in the state of proliferationcell culture5-Bromine added to the substancedeoxidationUridine(BrdU）BrdU in the DNA synthesis phase of cell division（Phase S）OfDNA semi reserved replicationDuring the process, it is involved in the newly synthesized DNA strand, and there are twocell cycleIn the case of using Giemsa dyemitosisstagePhase MThe cells were stained.Since BrdU participates in one single strand of DNA in one monomer of two sister chromatids, and two single strands in the other monomer, there is color difference between the two monomers (Figure 2).If twoChromatidThe corresponding discontinuous part of staining indicates that sister chromatids are exchanged.Under relatively constant culture conditions, the sister chromatid exchange (SCE) frequency of each cell is also relatively constantMutagen, you can see that SCE increases significantly (Figure 3).Detect with SCE rate in cellsEnvironmental mutagen, is a simple, fast and sensitive method.This method can be used for both in vitro cultured cells and in vivo cells. It can be used first to simulate the situation in vivo in the in vitro testmicrosomeThe enzyme activation system activates the analyte to further improve the reliability of detection.Each of the above methods has its advantages and disadvantages. Ames test is simple, sensitive, fast and economical, but the test object isprokaryoteThe mutagenic effects of many kinds of chemicals should only be preliminarily screened.micronucleusThe method is simple and easy, but only aschromosome aberrationSecondary indicators of.The sensitivity of SCE method is hundreds of times higher than that of conventional chromosome aberration analysis, which is simple and easy to operate. There is a stable spontaneous exchange frequency as the control, so it is more objective.But yesionizing radiationBut its sensitivity is not as good as the detection of chromosome aberration rate, so it still needs to be combined with chromosome aberration analysis.
OthersDNA damage repairAnd in vitro cell malignant transformation test.
Regularly check the workers exposed to toxic substances or radioactive substancesPeripheral blood, urine, feces andsemenSo as to monitor the genetic toxicological effects of harmful substances.Through these works, we can exploreOccupational cancerEtiology, evaluationIndustrial poisonAnd provide basis for formulating the maximum allowable concentration of industrial poisons.
Drug clinical transition
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Before clinical application, a new drug is usedtoxicologyIn addition to the detection ofSafe medicationProvide basis.
The current test method cannot be completely ruled outGenotoxicityThe substance with toxic substance is mistaken as toxic (false positive) and toxic substance is mistaken as non-toxic (false negative). Therefore, how to further design methods such as using sex cells as materials to eliminate the difference between in vitro and in vivo test results and improveaccuracy, research variouschemical substancesInteraction relationship and interaction timegenetic effect The impact of the toxin on the human body is a research topic faced by toxicology and genetics.Through these studies, we will also deepen our understanding of the chemical mechanism of the three effects of toxicological genetics.
