Differential effects of 2'-deoxyguanosine on peripheral blood mononuclear cell proliferation in healthy donors and Hashimoto's thyroiditis patients.
The aim of this study was to determine possible differences in peripheral blood mononuclear cells (PBMC) proliferation of healthy donors and Hashimoto's thyroiditis patients and whether a statistical approach to cell proliferation analysis might be used to discern the differences. The effect of a wide range of 2'-deoxyguanosine (dGuo) concentrations (0-1250 microM) on the mitogen-induced proliferation of PBMC was studied in healthy donors and Hashimoto's thyroiditis patients. Activity levels of purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) in PBMC were also measured. For the first time in a study of these models of dGuo toxicity in vitro, the analysis of polynomial trends of orders from 1 to 7 was applied to evaluate cell proliferation. A dose-dependent inhibition of mitogen-induced PBMC proliferation was observed in both groups. Data for linear trend established that PBMC from Hashimoto's thyroiditis patients were more sensitive to dGuo toxicity than PBMC from healthy donors. A positive quadratic trend at low dGuo doses was found in the cell proliferation of Hashimoto's thyroiditis patients. A decrease in PNP activity (P < 0.025) and an increase in ADA activity (P < 0.005) was observed in PBMC of Hashimoto's thyroiditis group. The differences in PBMC proliferation subjected to dGuo toxicity between the two groups could be related with the distinct pattern of purine salvage enzymes observed.
Covas
M I
MI
Servei de Laboratori, Hospital del Mar, Barcelona, Spain.
Esquerda
A
A
Arner
M
M
Sanz
F
F
Mahy
N
N
D000243:Adenosine Deaminase / Q000378:metabolism; D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D003849:Deoxyguanosine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism; D013967:Thyroiditis, Autoimmune / Q000097:blood*
D011683:Purine-Nucleoside Phosphorylase; D000243:Adenosine Deaminase; D003849:Deoxyguanosine