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From the histogram to see cycles and dose in radiation

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From the histogram to see cycles and dose in radiation

Analysis of relation between radiation-induced chromosome aberration (cycles) and the dose in Gy

Fang-I Chu

- Compare the cycle frequency under different dose in Gy(for 1, 2, and 4) for two aberration model
-breakage-and-reunion (BR model)

-recombinationalmisrepair (RM model)

and for the experimental data.

- Do this for both 2-cycles and n-cycles(n>2).

- Once we gain possible form of function for the BR model and RM model, we will be able to estimate the potential cycle frequency under different dose in Gy
- Help us to determine how aberration varies at different dose in Gy.

- A cycle of order n, characterized formally by the cyclic graph with 2n vertices, indicates that n chromatin breaks take part in a single irreducible reaction.
- Parenthetically grouped elements are arranged in the most conservative way possible, in order to bring an exchange to “closure”.
- Closure means all the elements involved in the exchange.

- Aberrations result from misrepair of DNA double strand breaks.(DSBs)
- DSBs: where both DNA sugar-phosphate backbones of a double helix are broken at nearby sites.
- Simple exchange, exchange requires 2 breaks. Which forms a 2-cycle or cycle of order 2 because there are 2 DSBsinvolved.(Giving 4 DSB ends)
- Complex exchange, exchange requires more than 2 breaks. Which forms a n-cycle or cycle of order n because there are nDSBsinvolved.(Giving 2n DSB ends)

- One-way exchanges, a simple terminal translocation-in which either centric or acentric elements were missing.
- Ex.(1’-X’)(1), and (12’T)(12-21’) both of which had missing elements that characterize them as so-called one-way exchange.
- Difference between incomplete changes and one way exchanges; the former is with one piece left alone, and the later with one piece attached but it is not visible.

- A truly incomplete exchange is identified when a painted fragment accompanied by a bicolor chromosome displays telomere signals on only one end of the fragment.
- When the painted fragment in the incomplete exchange displays telomere signals on both ends, the exchange is scored as a false incomplete exchange.
- An insertion may involve misrejoining of (a) two DSBs or (b) one DSB on the painted chromosome.

- We can think of exchange is an algorithm, that applied in RM model.
- Since simple exchange under RM model just involves 2 DSBs, it can easily be used to explain how exchange algorithm works.
- RM and BR are two ways how chromosomes rearrange after radiation; exchange theory is just develop to illustrate the process in between rearrange.

- Number of 2-cycle=total exchange-number of incomplete exchange-(interstitial deletions- number of acentricrings)+number observed of obligate 2-cycle
- Centric rings can be seen, so they are given in experimental data.
- We can compute number of acentric rings by introducing a relation parameter 1.2, which gives us:
- 1.2*number of centric rings =number of acentric rings

Using the table below to compute number of n-cycle(n>2,

3-cycle, 4-cycle,5-cycle.etc)

- First we can get the number of cycles under the 1 Gy,2 Gy,and 4Gy from the data table in Loucas and Cornforth paper.
- Then we calculate the value of cycle number/number of cells scored.
- The reason we do this is because we want to get the cycle number of per exposed cell versus dose; since we will simulate the cycles number under thousands of cells using CAS. To unitize the data we got from experiments help us compare on the same basis

- We failed to reproduce the histogram graph in Levy et al ‘s paper because CAS didn’t produce number of cycle during simulation.
- Need to run the data we get from CAS in another Java program to get the cycle number we need.
- Once we manage that, we will be able to get the exact histogram in Levy et al’s paper.

- We finally manage to transform the file from CAS to get it run in java this morning.
- However, there are still problems about the simulation, since we got the same number of cycles when we simulate different number of cells.
- Ex. For 20,000 cells at Gy1 we got 23 of 2-cycle and 1 of n-cycle, and we got the same result for 200 cells at Gy 1.

- The dosage of radiation doesn’t seem to influence the number of cycle linearly as the cycle structure increases.
- The patterns of cycle changes response to radiation dosage give the information about how DNA damage is. This could be a way of detecting early formation of tumor.
- There should be a more user-friendly software available to simulate cycle number. Currently CAS+Java only run in linux environment, and they require two stages of execution.

- Compute the cycle frequency of 3-cycles,4 cycles, 5 cycles, and n-cycles where n>5, instead of computing n-cycles where n>2.
- Draw histogram for about 4 group and the simple exchange group; also after running CAS, we will get comparison histogram for real data, BR, and RM for these five groups.
- Observe how the relation between cycle frequency and dose in Gy varies due to different number cycles.
- We are also interested in the changes in cycle frequency for higher dosage of radiation, like 6 Gy.8 Gy, 10 Gy.