COMPARISON OF EFFECTS OF UVA, UVB AND UVC ON GROWTH AND VIABILITY OF MITOGEN-STIMULATED HUMAN PERIPHERAL BLOOD CELLS

Abstract— Peripheral blood mononuclear cells were irradiated with UVA, UVB or UVC. The highest exposure dose used in each waveband reduced the number of viable cells to one-third the control cell population after 3 days in culture. Exposure of these cells to half as much UV from each waveband resulted in an equivalent or greater degree of inhibition of their proliferative response to mitogen as measured by lymphoblast transformation, [³H]-thymidine uptake and viable cell number on day 3 in culture. The pattern of inhibition was distinct for each waveband. UVA interfered with blastogenesis on the first 2 days of culture at doses which had considerably less effect on viable cell number. UVA also depressed the first round of DNA synthesis, which was detectable on the second day of culture. By day 3 in culture, however, the UVA-induced reduction in both the number of lymphoblasts and the uptake of [³H]-thymidine was a direct reflection of reduced numbers of viable cells. UVB did not interfere with blastogenesis in mitogen-stimulated cultures to the same degree as did UVA. Only the highest dose of UVB depressed blast transformation more than viable cell number on day 1; by day 2 lower doses were also inhibitory. In contrast UVC had little effect on blastogenesis at any time; a reduced number of lymphoblasts observed on days 2 and 3 in culture was a direct reflection of a reduced number of viable cells rather than a reduced percent of these cells undergoing blast transformation. As with UVA-irradiated, mitogen-stimulated cells, [³H]-thymidine uptake was also depressed in both UVB and UVC irradiated, mitogen-stimulated cells on day 2. However, only UVB continued to depress DNA synthesis more than viable cell number after 3 days of culture. These results suggest that UVA, UVB and UVC may interfere with any one or more of the signals involved in the response to mitogen, be they the recognition of mitogen by T cells or accessory cells, the transformation of lymphocytes into lymphoblasts or the activation of lymphoblasts to synthesize DNA.     

Targeted adenoviral vectors

The practical implementation of gene therapy in the clinical setting mandates gene delivery vehicles, or vectors, capable of efficient gene delivery selectively to the target disease cells. The utility of adenoviral vectors for gene therapy is restricted by their dependence on the native adenoviral primary cellular receptor for cell entry. Therefore, a number of strategies have been developed to allow CAR-independent infection of specific cell types, including the use of bispecific conjugates and genetic modifications to the adenoviral capsid proteins, in particular the fibre protein. These targeted adenoviral vectors have demonstrated efficient gene transfer in vitro, correlating with a therapeutic benefit in preclinical animal models. Such vectors are predicted to possess enhanced efficacy in human clinical studies, although anatomical barriers to their use must be circumvented.