Differential cytotoxicity in mouse epidermal JB6 cells: a potential mechanism for oxidant tumor promotion.
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 ([Ca2+]i) preceding bleb formation was observed in both p+ and p- cells by digital imaging fluorescence microscopy, elevated levels of [Ca2+]i were sustained longer in p- cells. This increase was dependent on the levels of extracellular ionized calcium ([Ca2+]e) in p+ but not p- cells. We conclude that the superior antioxidant defense or improved Ca2+ buffering of promotable clone 41 cells protects them from more severe deregulation of [Ca2+]i and, as a consequence, from excessive cytotoxicity after exposure to oxidant promoters.
Jain
P T
PT
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.
Chang
S H
SH
Berezesky
I K
IK
Amstad
P
P
Cerutti
P A
PA
Trump
B F
BF
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D002999:Clone Cells; D004249:DNA Damage; D005110:Extracellular Space / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D007424:Intracellular Fluid / Q000378:metabolism; D051379:Mice; D016877:Oxidants / Q000633:toxicity*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D012680:Sensitivity and Specificity; D012867:Skin / Q000166:cytology* / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D013481:Superoxides / Q000633:toxicity*; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism / Q000633:toxicity; D014970:Xanthines / Q000378:metabolism / Q000633:toxicity
D016877:Oxidants; D012333:RNA, Messenger; D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; D014969:Xanthine Oxidase; D002118:Calcium