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The effect of active oxygen generated by xanthine/xanthine oxidase on genes and signal transduction in mouse epidermal JB6 cells
Author(s) -
Singh Neeta,
Aggarwal Sudeepta
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910620120
Subject(s) - xanthine oxidase , protein kinase c , biology , tumor promotion , superoxide dismutase , signal transduction , catalase , microbiology and biotechnology , xanthine , biochemistry , enzyme , carcinogenesis , gene
To gain insight into the gene regulation and signal transduction effects of active oxygen in tumour promotion and progression, we studied the effect of active oxygen generated extracellulariy by xanthine/xanthine oxidase (X/XO) in promotion‐insensitive (P − ), promotion‐sensitive (P + ) and transformed (Tx) mouse epidermal JB6 cells. Active oxygen inhibited growth, particularly of P − cells and increased poly ADPR transferase activity and PKC activity more significantly in P − cells. No phenotypic differences in the distribution pattern of PKC isotypes α, β and γ were seen in JB6 cells. PKCα was expressed abundantly, whereas β and γ were not detected. Basal levels of the antioxidant enzymes catalase and CuZn. Superoxide dismutase were higher in P + and Tx cells. X/XO resulted in an initial decrease in the activity of these enzymes, followed by recovery or transient induction in Tx and P + cells. X/XO induced c‐myc and c‐ fos expression in JB6 cells, with c‐ fos induction being more pronounced in P − cells, whereas a biphasic increase in c‐ jun was seen in P + cells. These early genes may play a role in proliferation whereas post‐translational poly ADP‐ribosylation and, perhaps, phosphorylation suggest a genetic‐epigenetic mechanism in oxidant tumour promotion and progression. © 1995 Wiley‐Liss Inc.