| Melanoma is the most aggressive form of skin cancer and is notoriously resistant to all current modalities of cancer therapy by exploiting their intrinsic resistance to apoptosis and by reprogramming their proliferation and survival pathways during melanoma progression . The challenge is now to devise strategies potent enough to compensate or bypass these cell death defects and improve the actual poor prognosis of patients at late stages of the disease.Arsenic has a long history of use in Chinese and western medicine, but feel out of use in the mid-20lh century because of the unacceptable side effects that occurred at the doses that were thought to be necessary. The re-emergence of arsenic trioxide in clinical use is due largely to purification of this compound from traditional mixtures and the As2O3 definition of effective, low-dose regimens for the treatment of APL. Recently, the apoptosis As2O3-induced has been observed in many cancer cell lines, including esophaged carcinoma, gastric cancer, neuroblastoma lymphoid malignancies, and multiple myeloma2. Up to now, the role of AS2O3 on malignant melanoma has not been investigated.Depigmentation processes of vitiligo eliminate differentiaed melanocytes from the epidermis. When epidermal repigmentation occurs, it typically begains at the edges of hair follicles. This suggests that the follicle harbors a reservoir population of inactive or precursor melanocytes. Hair-follicle melanocytes consist of two morphologically and functionally different types:pigmented melanocytes (dendritic and dopo-positive), present in the infundibulum and bulb, and amelanotic melanocytes ( nondendritic and dopa-negative), present in the out root sheath of the middle and lower follicle. The later may provide a reservoir of melanocytes for hair bulbs during early anagen, hair regrowth in alopecia areata, and for repigmentation of the epidermis in vitiligo, burns, and dermabrasion.Availability of reliable methods of growing hair-follicle melanocytes in culture will lead to a better understanding of the role these cells in hair growth and disease.The epidermal melanin unit, a functional unit that produces and distributes melanin, is composed of one melanocyte and approximately 36 neighboring keratinocytes. Melanosomes are organells unique to melanocytes that function in the synthesis of melanin , a complex pigment involved in photoprotection of the skin through it's a bility to absorb and scatter light and reduce reactive oxygen species. In order to accomplish this, melanosomes must be transferred to epidermalkeratinocytes. Melanosomes are elliptical or spheroidal organelles that contain melanogenic enzyme and co-factor, including the tyrosinase gene familyof proteins and have been categorized as stage I-IV on the basis of their electron microscopic appearance and degree of melanizationPigment-loaded melanosomes translocate from their sites of origin in the perinuclear cytoplasm towards the melanocyte dendrite tips, then transferred into the recipient keratinocytes, where they are dispersed into the cytoplasm. The actui transfer of melanosomes into keratinocytes and the keratinocyte-melanocyte interactions during the transfer process are not well characterized.This thesis consists of four parts:Part 1: Studies of melanoma Cloundman S91 cell apoptosisOn the background of the known role of AS2O3 induced apoptotic effect on other types of tumor cells, we investigated a possible beneficial use of AS2O3 in the treatment of malignant melanoma, which incidence is growing at a faster rate than any other human malignancy, cis-dichlorodiamine platinum, CDDP is a effective drug against tumour, it could inhibit the DNA synthesis in tumour and induce cells apoptosis.In our study, Cloundman melanoma S91 cells are come from mice affected by malignant melanoma. We observed its apoptotic character by using morphological and biochemical parameters (nuclear DNA contentson flow cytometry and in situ TdT labeling reaction ) after in vitro treatment of AS2O3 at 1-5 umo...
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