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# Osteoarthritis

ACTSCI-AYRPBT

Use the information below as well as the previous passages to answer this question.

Osteoarthritis is an auto-immune bone disease. Very simply, the immune system of people with this condition attack the bone and cartilage cells in the joints, specifically in the knees and elbows, leaving the victims in crippling pain. It seems that when the immune system attacks the cells it leaves them in a condition known as “oxidative stress”. Cells in oxidative stress have great difficulty in keeping their telomeres healthy, and they shorten much more quickly than normal. These “ultra-short” telomeres lead to early cell death and the joints quickly become useless.

Telomeres are DNA sequences that repeat at the end of chromosomes. They protect chromosomes by attracting protein caps. These caps bind to the chromosomes and keep the long, thin threads of DNA from fraying. Usually the sequences are about 200 base pairs (bp) long and repeat 400-500 times at the end of each chromosome. When a cell is going to divide it enters a part of its life cycle called the synthesis phase. During this time a protein molecule called DNA polymerase will make a copy of each chromosome so that each new cell after division will have its own set of nucleotide bases. However DNA polymerase can never quite make it to the very end of each chromosome, so that after each cell division, the telomeres have shortened.

Eventually, the telomere sequences are too short to attract the protein caps, and without the proper protection, the delicate DNA threads fray, and the cell can no longer make the proteins it needs to divide, the cell enters a phase known as apoptosis, or programmed cell death.

Telomeres have attracted a great deal of research and much has been discovered their role in cell division. One of the first experiments was designed to elucidate exactly how much telomere DNA was needed in order for a cell to be healthy enough to divide. The researcher involved used cultures of human skin cells, called fibroblasts, to test the hypothesis. Skin cells were used because they are known to grow and divide actively for a number of generations. Cells were cultured in normal growth media (a cell sample is put in a petri dish and fed, the cells then divide on their own) and the number of cell divisions until apoptosis were measured. The length and condition of the telomeres were measured and recorded after the 10th division and then after apoptosis for each culture. The data is shown below:

Culture Plate # # of Cell Divisions until Apoptosis Telomere length after 10th division (bp) Telomere length after 20th division (bp) Telomere length just before apoptosis
1 23 8000 6000 3300
2 22 7500 5500 3450
3 24 8400 6400 3200
4 23 8000 6000 3300
5 26 9000 7000 3200

Use the information below, as well as the original passage, to answer questions 6-12.

Scientists have always had a great curiosity about cancer cells. When grown in culture dishes, cancer cells will divide indefinitely, unlike normal actively dividing cells such as fibroblasts, which eventually give out and enter apoptosis. As new research about telomeres became known, oncologists decided to re-examine cells from various abnormal growths. What they saw was stunning, the telomeres of these cells never shrank, nor did the ending DNA fibers ever fray. Whether it was the first division or the 500th, these cell telomeres retained their original base pair number and their ability to attract the protein caps necessary to keep their DNA strands from fraying.

The question that was quickly asked is what substance is responsible for keeping these abnormal cells telomere’s healthy? Four biological molecules known to exist in actively dividing cells were identified as possible candidates. A study of the concentrations of these molecules were undertaken to see if one could possibly be the telomeres “magic bullet”.

The data table below shows the results of a study using five different types of cells from human donors grown in the same culture medium. Chemical assays were used to measure the concentration of each molecule in each cell type.

$$\text{Concentration in ug/ml}$$

Cell Type Rate of Cell Division DNA Polymerase Housekeeping Protein Telomerase Spindle Microbtube Protein
Liver Medium 1.4 2.5 0.4 0.6
Neuron Very low 0.2 2.5 0.1 0.1
Fibrolast High 1.7 2.5 1.2 0.9
Bone Sarcoma Very High 2.1 2.5 6.1 0.9
Breast Carcinoma Very High 2.2 2.5 6.1 0.9

Which statement best compares the integrity of telomeres in a breast cancer cell vs. a knee joint cell of a patient with osteoarthritis?

A

The cancer cells have long, unhealthy telomeres, while the bone cells have very fit “ultra-short” telomeres.

B

Cancer cell telomeres stay undamaged and healthy, while the “ultra-short” telomeres of the bone cells allow these cells to have an increased life-span.

C

Cancer cells have telomeres and telomerase that allow for many cell divisions while the “ultra-short” telomeres of the bone cells cause rapid apoptosis.

D

‘’Ultra-short” telomeres in bone cells allow for rapid cell division while long telomeres in the cancer cells take much longer to divide.