Enhanced sensitivity to oxidant-induced micronucleus frequency in elderly individuals is not associated with glutathione S-transferase M1 (GSTM1) null genotype in lymphocytes.
BACKGROUND
A large number of studies have demonstrated that various kinds of DNA damage accumulate during aging and that oxidative stress possibly contributes to this process. Glutathione S-transferase M1 (GSTM1) can prevent their possible effects on DNA via detoxification of reactive substances that induced oxidative stress.


OBJECTIVE
To investigate the relationship between GSTM1 polymorphism and DNA sensitivity to oxidative stress with age, we used micronucleus (MN) frequency as a marker of DNA damage in lymphocytes from young and elderly subjects.


METHODS
This study was performed in 30 young (age range 20-36 years) and 30 elderly (age range 66-87 years) healthy individuals who were chosen on the basis of their GSTM1 genotype (15 GSTM1 null and 15 GSTM1 positive for each group). Lymphocytes were cultured after Ficoll isolation and treated for 48 h with a 30-muM dose of cumene hydroperoxide (CumOOH), a dose that does not decrease cell viability.


RESULTS
There was no significant difference in the MN frequency observed in control cultures from young and elderly individuals. However, the MN frequency in CumOOH-treated cultures was significantly higher in the elderly group than the young group (p < 0.001). No association was found between the GSTM1 phenotype and CumOOH-induced MN frequency.


CONCLUSIONS
The results suggest that lymphocytes of elderly individuals are more susceptible to in vitro MN induction by CumOOH. However, this difference in susceptibility is not explained by the lack of GSTM1.
Guven
Gulgun S
GS
Department of Medical Biology, Cerrahpasa Faculty of Medicine, University of Istanbul, Istanbul, Turkey.
Guven
Mehmet
M
Onaran
Ilhan
I
Tunckale
Aydin
A
Hacihanefioglu
Seniha
S
Ulutin
Turgut
T
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001555:Benzene Derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D004249:DNA Damage; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D015162:Micronucleus Tests; D011110:Polymorphism, Genetic
D001555:Benzene Derivatives; D005982:Glutathione Transferase; C007164:cumene hydroperoxide