Journal: A critical discussion on diet, genomic mutations and repair mechanisms
ID: 209058 • Letter: J
Question
Journal: A critical discussion on diet, genomic mutations and repair mechanisms in colon carcinogenesis. Toxicology Letters (2017)
Read the article above and answer the following questions.
Explain the role of the following elements in cancer.
mutations
oncogen
DNA methylation
DNA adducts
sister chromatid exchange
chromosomal aberrations
microsatellite instability
What is (are) the evidence to suggest that dietary compounds increase the risk of colon cancer?
What is the effect of mutation on KRAS and APC genes in colonic epithelial cells?
What is the role of genomic instability in cancer?
Explain what a telomere fusion is and its effect in human cells.
Explain the relation between diet, DNA damage, cell cycle, repair mechanisms and cancer.
Explanation / Answer
Mutation
Alteration or change is the sequence of DNA will leads to mutation in DNA. Mutation may be deletion, duplication, insertion or translocation. mutation in KRAS gene involve in colon carcinoma.
DNA methylation.
Methylation of DNA is process of addition of methyl group in DNA sequence but it dose not changes the sequence however it suppressed the transcription and the protein is not formed. Hence methylation in gene involves in colon cancer will alter the expression of that genes and leads to cancer.
DNA adduct
When DNA is bound to some agents or chemicals which causes cancer, are termed as DNA adduct.
Sister chromatid exchange
Exchange of genetic material between two identical sister chromatid, the mechanism is termed as sister chromatid exchange. This happened during the cell division, where genetic material is exchanges, during this process some gene may loss their expression and leads to cancer.
Chromosomal aberrations
Chromosomal aberrations like structural alteration (deletion, duplication or translocation) leads to cancer . eg translocation between chromosome number 9 and 22 leads to philadelphia chromosome (BCR/ABL), leads to cancer
Microsatellite instability
Microsatellite are repeated DNA motile presents on the telomeric end of chromosomes. Due to loss of DNA mismatch repair mechanism, DNA hyper mutatibity results in instability of microsatellite. Here abnormal (or mutated repeats) are continuously transcribed and leads to carcinogenic condition.
Diet with high level of N-nitroso compound will altered the DNA . hence its expression. Which is involve in colon cancer. So red meat whith high N-nitrosocompound, increase the risk of colon cancer, as compared to vegetarian diet.
Mutation in KRAS and APC gene in epithelium cells results in increase the rate of apoptosis which leads to abnormal cell death of epithelial cells. These genes are transcriptional factor hence mutation in any gene leads to inactivation of transcription.
Genomic instability termed as high frequencies of particular mutation in genome. High frequency of adenoma-carcinoma mutation in colon cancer leads to genomic instability in progeny or offsprings. Chromosomal instability, microsatellite instability and methylation instability are most common type of genomic instability observed in cancer.
Telomers are the end of chromosomes which are specially designed region that can prevent the chromosome to fuse with neighbor chromosome. but in telomere fusion, non- reciprocal translocation results in carcinomic condition in human.
G2 phase of cell cycle is the main phase of DNA repair and highest at M phase. Due to the diet containing N-nitrose compound, the DNA repair mechanism is impaired which leads to DNA damage in cell cycle. This type of DNA damage leads to cancer in later stage through chromosomal instability, mutation, DNA methylation etc.
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