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<p>Introduction of human chromosome 6 into malignant melanoma cell line UACC903 resulted in generation of the chromosome 6-mediated suppressed cell subline UACC903(+6) that displays attenuated growth rate, anchorage-dependency, and reduced tumorigenicity. We have showed that overexpression of a chromosome 6-encoded tumor suppressor gene led to partial suppression to UACC903 cell growth. We now describe the differences in apoptosis and cell cycle between UACC903 and UACC903(+6) before and after UV irradiation. MTT assay revealed 86.92&#177;8.24% of UACC903 cells viable, significantly (<i>p</i>&#60;0.01) higher than 48.76&#177;5.31% of UACC903(+6), at 24 hr after 254-nm UV irradiation (40 J/M²). Before UV treatment, flow cytometry analysis revealed 6.06&#177;0.20% apoptosis in UACC903, significantly (<i>p</i>=0.01) lower than 6.67&#177;0.15% in UACC903(+6). The G0/G1, S and G2/M phase cells of UACC903 were, respectively, 54.10&#177;0.59%, 22.31&#177;0.50% and 16.85&#177;0.25%, all significantly (<i>p</i>&#60;0.01) different from the corresponding percentages (58.82&#177;0.35%, 20.48&#177;0.05%, and 13.17&#177;0.45%) of UACC903(+6). After the UV treatment, UACC903 cells in apoptosis, G0/G1, S, and G2/M became 12.59&#177;0.17%, 38.90&#177;0.67%, 19.74&#177;0.70%, and 27.01&#177;0.66%, respectively, while UACC903(+6) cells were 24.16&#177;0.48%, 37.97&#177;0.62%, 19.20&#177;0.52%, and 15.69&#177;0.14%. TUNEL assay revealed 2.31&#177;0.62% apoptosis in UACC903, significantly (<i>p</i>&#60;0.01) lower than 9.60&#177;1.14% of UACC903(+6), and a linear and exponential increase of apoptosis, respectively, in response to the UV treatment. These results indicate that UACC903(+6) cells have a greater tendency to undergo apoptosis and are thus much more sensitive to UV irradiation. Our findings further suggest a novel mechanism for chromosome 6-mediated suppression of tumorigenesis and metastasis, i.e., through increased cell death.</p>