Cancer

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Chemosensitivity and Cancer Susceptibility

Cancer is defined as a malignant growth that tends to spread indefinitely and to reproduce itself. According to the American Cancer Society, 50 percent of American men and percent of American women get cancer in their lifetime. Though cancer differs in onset, growth rate, level of fatality, and cause, all cancers arise from cells that lost their normal growth controls. Normal cell growth is controlled by a variety of different growth factors, such as platelet-derived growth factor (PDGF). Cancer cells grow independent of normal growth signals.

Most cancer treatments aim to destroy the cancer cells using radiation (radiation therapy) or toxic chemicals (chemotherapy). Chemotherapy drugs interfere with the ability of a cancer to divide and reproduce its self. The name Chemotherapy literally means chemical therapy. Often if doctors can discover a tumor before metastasis occurs, doctors can try and remove the growth with out using cytotoxic drugs; immunosuppressive, immunomodulating chemicals.

There are many negative effects of radiation and chemotherapy. These treatments cause general weakness, weight loss, and hair loss. The administration of these drugs at high dose affects patients¡¦ red, white, and platelet cell levels in the body, the cells required to fight infection and to heal wounds. Therefore, a patient may not be able to recuperate from the treatment. To help patients survive high dose treatments, they might receive a bone marrow transplants from appropriate donors. A syringe withdraws a small amount of bone marrow from a donor¡¦s pelvic bone, and this gets injected into a patient whose ability to make new blood cells has been impaired by the cancer treatment. Many of these cancer therapies are themselves carcinogenic, a material or substance that produces or stimulates cancer. Yet, the drugs get used because of their ability to also control cancer. The probability of attacking a malignancy in ones body using these treatments proves much higher than the likely hood of developing a new cancer after effective treatment.

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Some individuals who receive radiation therapy or chemotherapy and kill the malignant cells, some years latter develop a second cancer. The cause for this particular reoccurrence of malignancy is not known. This unknown fact, leads to a simple question is there anything

unusual about the population of individuals who develop the second malignancy? Is their development of cancer random or are people susceptible to cancer induction?

A wide variation exists of cancer rates exist in individuals. In other words, individuals have varying chances of developing cancer. Because of an underlying alteration in their genome, some individuals find they are more inclined to get cancer. An alteration could be a mutation in a specific cancer gene, or it may be an alteration that affects the cells ability to repair damage to its DNA. All cancer cells hold mutations in genes that define a cells growth control factors.

Exposure to agents like radiation or chemicals that cause mutations can increase the probability of cancer. Individuals who are more sensitive to radiation or chemicals may be more likely to get cancer after exposure. In my project, I will test the hypothesis, that people who develop cancer following chemotherapy have sensitivity to the cancer-causing effects of the treatment. I will look at the chemosensitivity of cells from patients who developed cancer after chemotherapy, and compare that sensitivity to patients who were treated with the same drugs but did not get cancer. If one finds that the cells from patients who developed cancer are more sensitive to chemotherapy, then the hypothesis is correct. I will study 15 lines from patients who developed a second malignancy after treatment with cytoxan prior to bone marrow transplantation, and an equal number from patients who received the same treatment but did not develop cancer. These cell lines are immortal B cells derived from the blood of patients before any treatment.

I look at the effect of cytoxan on these cells. Cytoxan is used to decrease a patients¡¦ natural immunity before receiving a bone marrow transplant. Cytoxan causes a decrease in the number of all types of blood cells in a patients bone marrow. Bone marrow depression appears usually -14 days after individuals get treated with cytoxan.

Cytoxan

Cytoxan, which is a brand name for cyclophosphamide, causes a decrease in the number of all types of blood cells in a patients bone marrow.

In the lab, I will use two assays to measure sensitivity. The first will look at cell growth inhibition following treatment. Cells that are more sensitive to cytoxan should grow slower after treatment than cells that are resistant to cytoxan. The other assay, a chromosome assay, consists of looking for exchanges between sister chromatids (SCE) on the same chromosome following treatment with cytoxan.

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