PMID- 9200866
OWN - NLM
STAT- MEDLINE
DCOM- 19970828
LR  - 20190822
IS  - 0048-9697 (Print)
IS  - 0048-9697 (Linking)
VI  - 199
IP  - 1-2
DP  - 1997 Jun 20
TI  - A new concept for risk assessment of the hazards of non-genotoxic 
      chemicals--electronmicroscopic studies of the cell surface. Evidence for the 
      action of lipophilic chemicals on the Ca2+ signaling system.
PG  - 213-26
AB  - Recently, we presented evidence for the localization of components of the 
      cellular Ca2+ signaling pathway in microvilli. On stimulation of this pathway, 
      microvilli undergo characteristic morphological changes which can be detected by 
      scanning electron microscopy (SEM) of the cell surface. Here we show that both 
      receptor-mediated (vasopressin) and unspecific stimulation of the Ca2+ signaling 
      system by the lipophilic tumor promoters thapsigargin (TG) and 
      phorbolmyristateacetate (PMA) are accompanied by the same type of morphological 
      changes of the cell surface. Since stimulated cell proliferation accelerates 
      tumor development and sustained elevation of the intracellular Ca2+ 
      concentrations is a precondition for stimulated cell proliferation, activated 
      Ca2+ signaling is one possible mechanism of non-genomic tumor promotion. Using 
      isolated rat hepatocytes we show that all tested lipophilic chemicals with known 
      tumor promoter action, caused characteristic microvillar shape changes. On the 
      other hand, lipophilic solvents that were used as differentiating agents in cell 
      cultures such as dimethylsulfoxide (DMSO) and dimethylformamide also, failed to 
      change the microvillar shapes. Instead DMSO stabilized the original appearance of 
      microvilli. The used technique provides a convenient method for the evaluation of 
      non-genomic carcinogenicity of chemicals prior to their industrial application.
FAU - Gartzke, J
AU  - Gartzke J
AD  - Federal Institute for Occupational Safety and Health, Berlin, Germany.
FAU - Lange, K
AU  - Lange K
FAU - Brandt, U
AU  - Brandt U
FAU - Bergmann, J
AU  - Bergmann J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Sci Total Environ
JT  - The Science of the total environment
JID - 0330500
RN  - 0 (Alkanes)
RN  - 0 (Carcinogens)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Hexanones)
RN  - 0 (Receptors, Vasopressin)
RN  - 0 (Solvents)
RN  - 0 (Styrenes)
RN  - 3FPU23BG52 (Toluene)
RN  - 3K9958V90M (Ethanol)
RN  - 44LJ2U959V (Styrene)
RN  - 67526-95-8 (Thapsigargin)
RN  - 8696NH0Y2X (Dimethylformamide)
RN  - C0Z8884J3P (2,5-hexanedione)
RN  - JV0QT00NUE (undecane)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - S54S8B99E8 (Carbon Disulfide)
RN  - SY7Q814VUP (Calcium)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
MH  - Alkanes/toxicity
MH  - Animals
MH  - Calcium/*metabolism
MH  - Carbon Disulfide/toxicity
MH  - Carcinogens/*toxicity
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Cholinesterase Inhibitors/toxicity
MH  - Dimethyl Sulfoxide/toxicity
MH  - Dimethylformamide/toxicity
MH  - Ethanol/toxicity
MH  - Hexanones/toxicity
MH  - Liver/cytology/*drug effects/ultrastructure
MH  - Microscopy, Electron, Scanning
MH  - Microvilli/drug effects/metabolism/ultrastructure
MH  - Rats
MH  - Receptors, Vasopressin/drug effects
MH  - Risk Assessment
MH  - Signal Transduction/*drug effects
MH  - Solvents/*toxicity
MH  - Styrene
MH  - Styrenes/toxicity
MH  - Tetradecanoylphorbol Acetate/toxicity
MH  - Thapsigargin/toxicity
MH  - Toluene/toxicity
EDAT- 1997/06/20 00:00
MHDA- 1997/06/20 00:01
CRDT- 1997/06/20 00:00
PHST- 1997/06/20 00:00 [pubmed]
PHST- 1997/06/20 00:01 [medline]
PHST- 1997/06/20 00:00 [entrez]
AID - S0048-9697(97)05498-3 [pii]
AID - 10.1016/s0048-9697(97)05498-3 [doi]
PST - ppublish
SO  - Sci Total Environ. 1997 Jun 20;199(1-2):213-26. doi: 
      10.1016/s0048-9697(97)05498-3.