The effects of the broadband UVA radiation on myeloid leukemia cells: the possible role of protein kinase C in mediation of UVA-induced effects.
We examined the effects of broadband UVA radiation (320-400 nm) on a rat myeloid leukemia cell line-chloroma (ChL). A Phillips face tanner model HB 171/A was used as a light source. Chloroma were irradiated through a 5 mm thick glass filter that cut off all of the UVB contamination. The irradiances were measured, from 250 to 400 nm, with a well-characterized and calibrated double-grating spectroradiometer Optronic 742. The overall uncertainty of dose evaluation was estimated to be +/-15% (2 sigma). The cells were irradiated with UVA doses of 4 and 8 J/cm2 and cultured thereafter for 24 h. After this period of time, a marked decline up to 50% was observed in cell proliferation in UVA-irradiated ChL cultures. The cell proliferation decline was found to be caused by simultaneously occurring G2/M phase cell cycle arrest and apoptosis in part of the UVA-irradiated ChL population. Concomitantly, with the decline in cell proliferation, an increase was observed in the expression of the major histocompatibility (MHC) class I and II antigens. Because protein kinase C (PKC) is known to regulate cell proliferation, apoptosis and expression of MHC antigens, and because UVA was shown to regulate PKC activity/expression, we therefore examined whether UVA irradiation has any effect on the expression of isozymes of PKC. Western blots revealed that ChL express alpha, beta I, delta, epsilon, eta, and zeta/iota isozymes of PKC and that expression of all isozymes declined 24 h after UVA irradiation (8 J/cm2). Finally, PKC activation in ChL by exposure to phorbol ester caused cell cycle arrest in G1 phase but did not induce apoptosis. This suggests that the previously shown UVA-induced PKC activation in ChL might be responsible for the induction of MHC antigens but the simultaneously observed ChL apoptosis is likely to be mediated by PKC down-regulation. All together, our results suggest that UVA, at irradiance levels that resemble the outdoor exposure, may have profound effects on the immune-related properties of leukocytes. Thus, we speculate that in vivo the immune functions of leukocytes passing through dermal capillaries might be altered by exposure to solar UVA radiation.
Leszczynski
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Radiobiology Laboratory, Finnish Centre for Radiation and Nuclear Safety, Helsinki, Finland. Dariusz.Leszczynski@stuk.fi
Fagerholm
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Leszczynski
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D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D007527:Isoenzymes / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology*; D008285:Major Histocompatibility Complex; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D007527:Isoenzymes; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate