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Differential cytotoxicity in mouse epidermal JB6 cells: A potential mechanism for oxidant tumor promotion
Author(s) -
Jain Pramod T.,
Chang Seung H.,
Berezesky Irene K.,
Amstad Paul,
Cerutti Peter A.,
Trump Benjamin F.
Publication year - 1994
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940110307
Subject(s) - biology , cytotoxicity , xanthine oxidase , tumor promotion , clone (java method) , microbiology and biotechnology , cell culture , cytosol , biochemistry , in vitro , carcinogenesis , dna , genetics , gene , enzyme
It has been suggested that superior antioxidant defense systems protect promotion‐sensitive (p + t) mouse epidermal JB6 clone 41 cells from excessive deleterious effects of oxidants, allowing their clonal expansion in contrast to that of promotion‐resistant (p—) clone 30 cells. In support of this concept, we report that oxidants produced by xanthine/xanthine oxidase cause more cytotoxicity, cellular damage, and cell death in p—cells. Cell surface blebbing, an early morphological consequence of oxidative injury, was detected in cultures grown on glass coverslips. While a rise in cytosolic ionized calcium ([Ca 2+ ] i ) preceding bleb formation was observed in both p+ and p— cells by digital imaging fluorescence microscopy, elevated levels of [Ca 2+ ] i were sustained longer in p— cells. This increase was dependent on the levels of extracellular ionized calcium ([Ca 2+ ] e ) in p+ but not p— cells. We conclude that the superior antioxidant defense or improved Ca 2+ buffering of promotable clone 41 cells protects them from more severe deregulation of [Ca 2+ ] i and, as a consequence, from excessive cytotoxicity after exposure to oxidant promoters. ©1994 Wiley‐Liss, Inc.