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Life Extension Magazine

May 9, 2000

National Academy of Sciences References


21. Res Commun Chem Pathol Pharmacol 1992 Feb;75(2):251-4Antioxidants and UV-induced genotoxicity.Dreosti I, McGown MDivision of Human Nutrition, CSIRO (Australia), Adelaide.

Genetic damage in mouse splenocytes exposed to UVA and UVB irradiation in vitrowas demonstrated to be expressed as micronuclei in cell cultures stimulated todivide and blocked at cytokinesis. Because of the involvement of active forms ofoxygen in UV-related genotoxicity, the present study investigated thephotoprotective effect with respect to micronuclei, of the antioxidant couplevitamin C/E administered to mice in vivo or to cell cultures in vitro prior toUV irradiation of splenocytes in vitro. Significant protection was observed inboth studies by antioxidant pretreatment, which highlights the importance ofactive oxygen in UV-induced genetic damage and suggests a significant role fornutritional antioxidants in sun damage prophylaxis.

22. Am J Surg 1991 Oct;162(4):294-8Effects of N-acetyl-L-cysteine and ascorbic acid on mutagen-induced chromosomalsensitivity in patients with head and neck cancers.Trizna Z, Schantz SP, Hsu TCDepartment of Head and Neck Surgery, University of Texas M. D. AndersonCancerCenter, Houston.

The protective effect of N-acetyl-L-cysteine (NAC) and ascorbic acid onmutagen-induced chromosomal breakage was determined using human lymphoblastoidcell lines as well as freshly cultured lymphocytes from patients with head andneck malignancies and healthy control subjects. Mutagen sensitivity wasdetermined using the previously described bleomycin exposure assay. Thetoxicities of different concentrations of NAC and ascorbic acid, as well as boththe preincubation and dose-dependent protective effects of these two agents,were analyzed. Both test drugs proved to be effective in diminishingmutagen-induced chromatid breakage in established lymphocyte cell lines. Infreshly cultured lymphocytes, NAC given in doses ranging from 0.1 to 10 mmol/Ldecreased the number of mutagen-induced breaks per cell in a range from 23% to73%, and ascorbic acid decreased chromosomal breakage by 21% to 58% in a doserange from 0.01 to 1 mmol/L. The results of this study demonstrate theprotective effect mediated in vitro by both NAC and ascorbic acid againstmutagen-induced chromosomal damage. A similar in vivo phenomenon may explain thedifferences in occurrence of head and neck cancer between populations withdifferent dietary backgrounds.

23. Mutat Res 1989 Oct;224(2):247-52Vitamin C intake influences the bleomycin-induced chromosome damage assay:implications for detection of cancer susceptibility and chromosome breakagesyndromes.Pohl H, Reidy JAGenetics Branch, Centers for Disease Control, Atlanta, GA 30333.

Supplementation with 1 g of vitamin C (ascorbic acid) per day decreased theamount of chromosome damage induced in lymphocytes by an exposure to bleomycinduring the last 5 h of cell culture. We did not see such changes in lymphocytesfrom control individuals samples at the same time but not taking vitamin Csupplements. This bleomycin assay has been proposed as a test for cancersusceptibility. A similar assay for genetic instability may be useful indetecting heterozygotes for chromosome-breakage syndromes (for example, Fanconianemia or ataxia telangiectasia). Even though our sample size is small and ourresults should be interpreted cautiously, statistically significant effects werefound with vitamin C supplementation. It would, therefore, be prudent toconsider dietary and perhaps other lifestyle factors when interpreting ofresults from this bleomycin assay and related assays for genetic instability.

24. Mutat Res 1989 Oct;224(2):247-52Vitamin C intake influences the bleomycin-induced chromosome damage assay:implications for detection of cancer susceptibility and chromosome breakagesyndromes.Pohl H, Reidy JAGenetics Branch, Centers for Disease Control, Atlanta, GA 30333.

Supplementation with 1 g of vitamin C (ascorbic acid) per day decreased theamount of chromosome damage induced in lymphocytes by an exposure to bleomycinduring the last 5 h of cell culture. We did not see such changes in lymphocytesfrom control individuals samples at the same time but not taking vitamin Csupplements. This bleomycin assay has been proposed as a test for cancersusceptibility. A similar assay for genetic instability may be useful indetecting heterozygotes for chromosome-breakage syndromes (for example, Fanconianemia or ataxia telangiectasia). Even though our sample size is small and ourresults should be interpreted cautiously, statistically significant effects werefound with vitamin C supplementation. It would, therefore, be prudent toconsider dietary and perhaps other lifestyle factors when interpreting ofresults from this bleomycin assay and related assays for genetic instability.

25. Mutat Res 1985 Mar;149(1):83-94The action of anticlastogens in human lymphocyte cultures and their modificationby rat-liver S9 mix. II. Studies with vitamins C and E.Gebhart E, Wagner H, Grziwok K, Behnsen H

The action of vitamins C (VC) and E (VE) on the clastogenic activity of trenimon(TR), cyclophosphamide (CP) and bleomycin (BM) was tested on cultures of humanperipheral blood lymphocytes with and without addition of rat-liver S9 mix. Inaddition, the influence of both anticlastogens on the SCE-inducing activity ofTR and CP was examined under the same conditions. A distinct dose-dependentanticlastogenic effect of VC was detected in the action of long-term treatment(24 h) with TR, if the vitamin was added to the cultures simultaneously with orbefore the clastogen. In the short-term tests (2 or 3 h clastogen treatmentending 23 h or 21 h before harvesting) simultaneous addition of both vitaminsdid reduce the chromosome-damaging action of TR whether S9 mix was present orabsent. While VC also decreased the frequency of chromosome damage induced byS9-mix-activated CP, VE was inactive under the same conditions. Neither vitaminsignificantly affected the chromosome-breaking activity of BM if S9 mix wasabsent, but they increased the clastogenicity of BM metabolized by S9 mix. Incontrast to their anticlastogenic efficacy neither of the vitamins displayed anysignificant anti-SCE effect, nor were they active in affecting the inhibition ofcell proliferation caused by TR or CP.

26. Mutat Res 1998 Nov 9;419(1-3):137-43Effects of high doses of vitamins C and E against doxorubicin-inducedchromosomal damage in Wistar rat bone marrow cells.Antunes LM, Takahashi CSDepartamento Genetica, Faculdade Med. de Ribeirao Preto-USP, Av. Bandeirantes,3900, 14049-900, Ribeirao Preto, SP, Brazil. lugreggi@fcfrp.usp.br

Doxorubicin (DXR) is one of the major antitumoral agents available for clinicaluse. In addition to intercalating into the DNA molecule, this drug generatesfree radicals. Vitamins C (VC) and E (VE) can protect normal cells from thedamage caused by radicals without interfering with the cytotoxicity of DXRagainst tumors. The objective of the present study was to investigate thepossible protective effect of VC and/or VE on mammalian cells treated with DXRin vivo. Animals treated with the lowest doses of VC and/or VE, alone or incombination, plus a single dose of DXR presented a statistically significantreduction in total number of chromosome aberrations and in number of abnormalmetaphases. The highest vitamin doses tested caused no changes in the parametersanalyzed when compared with control. Under the present experimental conditions,the efficiency of VC and/or VE in protecting against chromosome damage wasdependent on the dose used. Copyright 1998 Elsevier Science B.V.

27. Teratog Carcinog Mutagen 1998;18(4):153-61Protective effects of the amino acid glutamine and of ascorbic acid againstchromosomal damage induced by doxorubicin in mammalian cells.Tavares DC, Cecchi AO, Antunes LM, Takahashi CSDepartamento de Genetica, Faculdade de Medicina de Ribeirao Preto, Universidadede Sao Paulo, Brasil. dtavares@spider.usp.br

The interaction of antioxidants can provide an essential protection against thedamaging effects of free radicals. Beneficial interactions includeradioprotection, protection against acute toxicity of chemicals, andantimutagenic and anticarcinogenic activity. The present study was undertaken toevaluate the protective effect of the amino acid glutamine (GLN) and ascorbicacid (AA) on the frequency of chromosomal aberrations induced by theantineoplastic agent doxorubicin (DXR). These micronutrients were testedseparately and simultaneously in Wistar rat bone marrow and Chinese hamsterovary (CHO) cells. The treatments with GLN and/or AA significantly decreased thefrequency of DXR-induced clastogenic damage in both test systems.

28. Carcinogenesis 1997 Jan;18(1):223-8Ascorbic acid and beta-carotene as modulators of oxidative damage.Cozzi R, Ricordy R, Aglitti T, Gatta V, Perticone P, De Salvia RDipartimento di Biologia, Universita degli Studi Roma Tre, Italy.

Naturally occurring antioxidants are extensively studied for their capacity toprotect organisms and cells from damage induced by oxygen reactive species. Infact, oxidative stress is considered a cause of aging, degenerative disease andcancer. We have focused our attention on two agents, ascorbic acid andbeta-carotene, commonly considered to be antioxidants, but whose protectiveactivity against cancer is insufficiently known. This paper reports on theability of these agents to act against damage induced by H2O2 and bleomycin, inChinese hamster ovary cells cultivated in vitro. Cytogenetic andcytofluorimetric analyses were performed. Both vitamins proved effective inreducing H2O2-induced sister chromatid exchanges, but increased H2O2- andbleomycin-induced chromosomal aberrations. Cytofluorimetric data, in contrast,showed that ascorbic acid and beta-carotene act as scavengers of endogeneous andH2O2-induced oxygen species.

29. Radiats Biol Radioecol 1995 Sep-Oct;35(5):726-9[The anticlastogenic effect of ascorbic acid in relation to the damages inducedin human lymphocytes by the photomutagenic action of 8-methoxypsoralen and byammonium molybdate].[Article in Russian]Makedonov GP, Bobyleva LA, Chekova VV, Zasukhina GD

In experiments with cultured human lymphocytes anticlastogenic effect ofascorbic acid (AA) with respect to photomutagenic action of 8-methoxypsoralen(8-MOP) and ammonium molibdenate (Mo) was studied. It was found that AAeffectively protected from mutagenic action of Mo. Effective protection of cellsfrom 8-MOP monoadducts and DNA interstrand links was also observed.

30. Radiats Biol Radioecol 1995 Sep-Oct;35(5):726-9[The anticlastogenic effect of ascorbic acid in relation to the damages inducedin human lymphocytes by the photomutagenic action of 8-methoxypsoralen and byammonium molybdate].[Article in Russian]Makedonov GP, Bobyleva LA, Chekova VV, Zasukhina GD

In experiments with cultured human lymphocytes anticlastogenic effect ofascorbic acid (AA) with respect to photomutagenic action of 8-methoxypsoralen(8-MOP) and ammonium molibdenate (Mo) was studied. It was found that AAeffectively protected from mutagenic action of Mo. Effective protection of cellsfrom 8-MOP monoadducts and DNA interstrand links was also observed.