SCE's as possible tools for detecting cancers

Cancer is spreading widely across the world and is affecting majority of the people. It is one of the top 10 causes of death in the whole world. Detecting cancer in the early stages can save lives. However it is a very tricky thing to detect it early and in most of the cases, it takes time to show the symptoms. The actual reason behind the spread of this deadly disease is unknown, though many factors that have been responsible for causing cancer, have been reported. Various types of cancers such as lung cancer, breast cancer, prostate cancer, leukemias etc have been reported. The treatment strategies for controlling cancer are very painful and often lead to demotivate the patient. We need more advancement in detection and diagnosis in cancer so that new treatment strategies can be planned. One of the main causes behind spread of the cancer cells is a genetic cause, probably a mutation. Therefore, genetics can be promising for detecting cancer cells in the body.  
Sister chromatid exchanges (SCE’s) are exchanges of genetic material between two sister chromatids. Excessive SCE’s are responsible for bringing out various abnormalities such as chromosome instability syndromes and cancers. They are caused due to exposure to chemical mutagens, radiations or some alkylating agents. FPG and CO-FISH techniques can be used to visualize sister chromatid exchanges, hence we can estimate that if more numbers of SCE’s are found in a cell, there is something abnormal , may it be a cancer or  some chromosomal aberration.  

Significance of SCE’s:

Normally 10 SCE’s per cell are observed but the number exceeds if there is some abnormality. For example Bloom’s syndrome is a rare chromosome instability syndrome which results due to BLM gene mutations. In this case, elevated levels of sister chromatid exchanges are observed, along with increased chromosome breakage and rearrangements. SCE’s can be used for genotoxicity tests of reversible damages. It has also been used as a marker for genomic instability and mutagenic studies (pertaining to tumours and cancers). 

Agents that increase the number of SCE's per cell:

a) Physical mutagens such as radiations

b) Agents that produce single strand breaks and double strand breaks and interstrand cross links, DNA damage pertaining to replication fork.

c) DNA repair proteins that sometimes lead to formation of SCE’s.

d) Certain number of homologous recombination, non homologous end joining and nucleotide excision repair pathways can also influence SCE’s.

e) Mitomycin C, an ICL forming protein, produces large amount of reactive oxygen species. These ROS can damage DNA by direct oxidation of DNA strand itself.

f) MNNG(N-methyl-N- Nitrosguanidine ) is an alkylating agent that is another common SCE inducer.

SCE’s at telomeric regions:

SCE’s at telomeric regions can be detected using CO-FISH technique (chromosome orientation fluorescence insitu hybridisation).CO-FISH can be used to detect chromosomal inversions associated with isochromosomes and pericentric inversion. It has been investigated that SCE’s at telomeric regions are associated with ageing.

These SCE’s can be shown by differences in uptake of certain stains by two chromatids of each metaphase chromosome by two rounds of cell division in presence of Thymidine analogue 5- Bromodeoxyuridine(5’ BUdR) , which gets incorporated in newly synthesized DNA. In case of Xeroderma pigmentosum , another chromosome instability disorder, which results due to nucleotide excision repair defect, SCE’s are only apparent after the cells are exposed to UV light. Thus they are also involved in chromosome breakage. SCE’s involve breakage of both DNA strands, followed by an exchange of whole DNA duplex. This process occurs during the S phase of cell cycle. The genetic makeup of a cell is not altered if a SCE takes place at identical sites. But if it takes place at different sites, it results into duplication of a segment on one chromatid and deletion from the other chromatid. SCE test is usually performed on human peripheral blood lymphocytes.