M. Wojewodzka et al., CALCIUM-ANTAGONIST, TMB-8, PREVENTS THE INDUCTION OF ADAPTIVE RESPONSE BY HYDROGEN-PEROXIDE OR X-RAYS IN HUMAN-LYMPHOCYTES, International journal of radiation biology, 66(1), 1994, pp. 99-109
Citations number
40
Categorie Soggetti
Radiology,Nuclear Medicine & Medical Imaging","Nuclear Sciences & Tecnology
Treatment of human lymphocytes with hydrogen peroxide (10 mu M, 30 min
, 37 degrees C in PBS) or with 1 cGy X-rays evoked about a 30% decreas
e in the frequency of micronuclei upon subsequent X-irradiation (1.5 G
y). In addition to a lower micronuclei frequency, we also found an inc
rease in the sedimentation distance of the nucleoids, when measured 90
min (duration of the isolation procedure carried out at 4 degrees C)
after the adaptive dose (hydrogen peroxide or X-rays) and preceding th
e challenge dose. To test whether Ca2+ is involved in the induction of
the adaptive response pathway, we treated cells with the calcium chel
ator, EGTA. When EGTA was given at the same time as the adaptive dose,
it prevented the development of the adaptive response. In addition, t
he calcium antagonist, TMB-8, also prevented the development of the ad
aptive response as it prevented the reduction of both micronuclei and
increased nucleoid sedimentation. Cellular treatment with TMB-8 increa
sed the free [Ca2+] by 40%, when given together with hydrogen peroxide
. The faster sedimenting nucleoids from adapted cells were also examin
ed by ethidium bromide titration; there was no indication of any chang
e in supercoil density or loop size. Psi-tectorigenin, an inhibitor of
phosphatidylinositol turnover, did not modify the adaptive response,
indicating that inositol (1,4,5)-trisphosphate is not involved in the
induction of the adaptive response, but free Ca2+ ions are.