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Title: Clastogenic factors in the plasma of Chernobyl accident recovery workers: Anticlastogenic effect of Ginkgo biloba extract

Abstract

Clastogenic factors are found in the plasma of persons irradiated accidentally or therapeutically. They persisted in the plasma of A-bomb survivors over 30 years. Clastogenic factors were found in 33 or 47 Chernobyl accident recovery workers (often referred to as liquidators) in a previous study. In the present study, we show that there is a positive correlation between clastogenic activity and dose and that these biomarkers of oxidative stress can be influenced successfully by appropriate antioxidant treatment. With the authorization of the Armenian Ministry of Health, 30 workers were treated with antioxidants from Ginkgo biloba leaves. The extract EGb 761 containing flavonoids and terpenoids was given at a daily dose of 3 x 40 mg (Tanakan, IPSEN, France) during 2 months. The clastogenic activity of the plasma was reduced to control levels on the first day after the end of the treatment. A 1-year follow-up showed that the benefit of the treatment persisted for at least 7 months. One-third of the workers again had clastogenic factors after 1 year, demonstrating that the process which produced clastogenic factors continued. However, the observation that antioxidants do not have to be given continuously is encouraging for intervention trials on a large-scale basis. Thesemore » appear justified, since clastogenic factors are thought to be risk factors for the development of late effects of irradiation. 43 refs., 6 tabs.« less

Authors:
; ;  [1]
  1. Universite Paris (France) [and others
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
183326
Resource Type:
Journal Article
Resource Relation:
Journal Name: Radiation Research; Journal Volume: 144; Journal Issue: 2; Other Information: PBD: Nov 1995
Country of Publication:
United States
Language:
English
Subject:
56 BIOLOGY AND MEDICINE, APPLIED STUDIES; ANTIOXIDANTS; THERAPEUTIC USES; PLASMA; BIOLOGICAL RADIATION EFFECTS; RADIATION DOSES; BIOLOGICAL MARKERS; A-BOMB SURVIVORS; IRRADIATION; DOSE-RESPONSE RELATIONSHIPS; CHERNOBYLSK-4 REACTOR; REACTOR ACCIDENTS

Citation Formats

Emerit, I., Levy, A., and Cernjavski, L. Clastogenic factors in the plasma of Chernobyl accident recovery workers: Anticlastogenic effect of Ginkgo biloba extract. United States: N. p., 1995. Web. doi:10.2307/3579259.
Emerit, I., Levy, A., & Cernjavski, L. Clastogenic factors in the plasma of Chernobyl accident recovery workers: Anticlastogenic effect of Ginkgo biloba extract. United States. doi:10.2307/3579259.
Emerit, I., Levy, A., and Cernjavski, L. 1995. "Clastogenic factors in the plasma of Chernobyl accident recovery workers: Anticlastogenic effect of Ginkgo biloba extract". United States. doi:10.2307/3579259.
@article{osti_183326,
title = {Clastogenic factors in the plasma of Chernobyl accident recovery workers: Anticlastogenic effect of Ginkgo biloba extract},
author = {Emerit, I. and Levy, A. and Cernjavski, L.},
abstractNote = {Clastogenic factors are found in the plasma of persons irradiated accidentally or therapeutically. They persisted in the plasma of A-bomb survivors over 30 years. Clastogenic factors were found in 33 or 47 Chernobyl accident recovery workers (often referred to as liquidators) in a previous study. In the present study, we show that there is a positive correlation between clastogenic activity and dose and that these biomarkers of oxidative stress can be influenced successfully by appropriate antioxidant treatment. With the authorization of the Armenian Ministry of Health, 30 workers were treated with antioxidants from Ginkgo biloba leaves. The extract EGb 761 containing flavonoids and terpenoids was given at a daily dose of 3 x 40 mg (Tanakan, IPSEN, France) during 2 months. The clastogenic activity of the plasma was reduced to control levels on the first day after the end of the treatment. A 1-year follow-up showed that the benefit of the treatment persisted for at least 7 months. One-third of the workers again had clastogenic factors after 1 year, demonstrating that the process which produced clastogenic factors continued. However, the observation that antioxidants do not have to be given continuously is encouraging for intervention trials on a large-scale basis. These appear justified, since clastogenic factors are thought to be risk factors for the development of late effects of irradiation. 43 refs., 6 tabs.},
doi = {10.2307/3579259},
journal = {Radiation Research},
number = 2,
volume = 144,
place = {United States},
year = 1995,
month =
}
  • In the present study, we investigated the effect of Ginkgo biloba extracts and some of its individual constituents on the catalytic activity of human cytochrome P450 enzymes CYP1B1, CYP1A1, and CYP1A2. G. biloba extract of known abundance of terpene trilactones and flavonol glycosides inhibited 7-ethoxyresorufin O-dealkylation catalyzed by human recombinant CYP1B1, CYP1A1, and CYP1A2, and human liver microsomes, with apparent K {sub i} values of 2 {+-} 0.3, 5 {+-} 0.5, 16 {+-} 1.4, and 39 {+-} 1.2 {mu}g/ml (mean {+-} SE), respectively. In each case, the mode of inhibition was of the mixed type. Bilobalide, ginkgolides A, B, C,more » and J, quercetin 3-O-rutinoside, kaempferol 3-O-rutinoside, and isorhamentin 3-O-rutinoside were not responsible for the inhibition of CYP1 enzymes by G. biloba extract, as determined by experiments with these individual chemicals at the levels present in the extract. In contrast, the aglycones of quercetin, kaempferol, and isorhamentin inhibited CYP1B1, CYP1A1, and CYP1A2. Among the three flavonol aglycones, isorhamentin was the most potent in inhibiting CYP1B1 (apparent K {sub i} = 3 {+-} 0.1 nM), whereas quercetin was the least potent in inhibiting CYP1A2 (apparent K {sub i} 418 {+-} 50 nM). The mode of inhibition was competitive, noncompetitive, or mixed, depending on the enzyme and the flavonol. G. biloba extract also reduced benzo[a]pyrene hydroxylation, and the effect was greater with CYP1B1 than with CYP1A1 as the catalyst. Overall, our novel findings indicate that G. biloba extract and the flavonol aglycones isorhamnetin, kaempferol, and quercetin preferentially inhibit the in vitro catalytic activity of human CYP1B1.« less
  • The present cell culture study investigated the effect of Ginkgo biloba extract pretreatment on acetaminophen toxicity and assessed the role of ginkgolide A and cytochrome P450 3A (CYP3A) in hepatocytes isolated from adult male Long-Evans rats provided ad libitum with a standard diet. Acetaminophen (7.5-25 mM for 24 h) conferred hepatocyte toxicity, as determined by the lactate dehydrogenase (LDH) assay. G. biloba extract alone increased LDH leakage in hepatocytes at concentrations {>=} 75 {mu}g/ml and {>=} 750 {mu}g/ml after a 72 h and 24 h treatment period, respectively. G. biloba extract (25 or 50 {mu}g/ml once every 24 h formore » 72 h) potentiated LDH leakage by acetaminophen (10 mM for 24 h; added at 48 h after initiation of extract pretreatment). The effect was confirmed by a decrease in [{sup 14}C]-leucine incorporation. At the level present in a modulating concentration (50 {mu}g/ml) of the extract, ginkgolide A (0.55 {mu}g/ml), which increased CYP3A23 mRNA levels and CYP3A-mediated enzyme activity, accounted for part but not all of the potentiating effect of the extract on acetaminophen toxicity. This occurred as a result of CYP3A induction by ginkgolide A because triacetyloleandomycin (TAO), a specific inhibitor of CYP3A catalytic activity, completely blocked the effect of ginkgolide A. Ginkgolide B, ginkgolide C, ginkgolide J, quercetin, kaempferol, isorhamnetin, and isorhamnetin-3-O-rutinoside did not alter the extent of LDH leakage by acetaminophen. In summary, G. biloba pretreatment potentiated acetaminophen toxicity in cultured rat hepatocytes and ginkgolide A contributed to this novel effect of the extract by inducing CYP3A.« less
  • Ginkgo biloba L. (maidenhair tree) was studied in polluted and relatively clean habitats of West Tennessee. In spite of its known resistance to smog and automobile exhaust fumes, it exhibited a decrease in leaf length, leaf width, and petiole length in polluted habitats. Furthermore, there was a definite trend towards lower stomatal density along the pollution gradient in selected habitats.
  • A 10-year old completed landfill in New Jersey consisting of 9 m (depth) of refuse covered with 15-25 cm of soil was cleared of debris and vegetation and covered with 30 cm of subsoil and 15-25 cm of topsoil. Nineteen coniferous and broadleaved species were planted on the landfill and on a control site in 1975, and trees were maintained and growth and condition monitored over 4 years. On the basis of shoot length and stem area increase, the most successful of the surviving trees were Nyssa sylvatica, Picea abies and Ginkgo biloba, in decreasing order of tolerance. Tolerance ofmore » landfill conditions appeared to be greatest in those species with low water requirements, a slow growth rate, high acid tolerance and a shallow root system. (Refs. 11).« less