Dynamics of reactive oxygen intermediate production in human glioma: n-6 essential fatty acid effects.
BACKGROUND
Reactive oxygen intermediates (ROIs) are important signals controlling cell growth and cell death. Local essential fatty acid (EFA) deficiencies in tumour cells may limit tumour ROI generation. This deficiency may be rectified by the addition of exogenous EFA.


METHODS
The n-6 EFA effects on tumour ROIs were analysed in terms of kinetics, dose-response and individual cell type responses using flow cytometry of intracellular 2',7'-dichlorofluorescin oxidation. ROI formation in 30 gliomas and five paired samples of normal brain tissue, > 500 000 cells per specimen, was analysed every 10 s for 0-25 min.


RESULTS
Tumour cell basal ROI was lower than normal brain tissue ROI from the same subjects (P < 0.00002). Normal and tumour cell ROIs were stimulated by 4-40 micromol L-1 n-6 EFAs, arachidonic acid (AA) and gamma-linolenic acid (GLA). The stimulated ROI rate was exponential, with the maximum dependent on EFA concentration and tumour grade.


CONCLUSIONS
EFAs stimulated tumour cells more than normal cells (P < 0.0000017, n = 71) and increased ROIs in glial fibrillary acidic protein-positive cells in tumours. This indicated high sensitivity of glioma cell ROIs to n-6 EFAs.
Leaver
H A
HA
Department of Pharmacology, University of Edinburgh, UK. pengl@netcomuk.co.uk
Williams
J R
JR
Ironside
J W
JW
Miller
E P
EP
Gregor
A
A
Su
B H
BH
Prescott
R J
RJ
Whittle
I R
IR
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017965:gamma-Linolenic Acid / Q000494:pharmacology
D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D005904:Glial Fibrillary Acidic Protein; D017382:Reactive Oxygen Species; D017965:gamma-Linolenic Acid