CAROTENOID/RETINOID MODULATION OF CELLULAR REDOX STATUS AND CANCER
CAROTENOID/RETINOID MODULATION OF CELLULAR REDOX STATUS AND CANCER
批准号:
6293840
负责人:
JOHN EDGAR FRENCH
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
acetylcysteine antioxidants apoptosis benzopyrenes biological signal transduction carcinogenesis inhibitor carotenoids chemical carcinogenesis cysteine dietary supplements disease /disorder model gene expression genetically modified animals laboratory mouse lymphoma microarray technology molecular oncology neoplasm /cancer genetics neoplastic process nutrient interaction nutrition aspect of cancer nutrition related tag oxidation reduction reaction retinoids skin neoplasms
中文摘要
n -乙酰半胱氨酸(NAC)和4-羟基苯基视黄酰胺(4-
英文摘要
Both N-acetyl cysteine (NAC) and 4-hydroxyphenylretinamide (4-
HPR) were found to have significant effects on the
multiplicity of TPA-induced papillogenesis in male TG.AC mice.
4 -HPR was found to inhibit papillogenesis and the inhibition
was only observed if present early in papillogenesis. Follow-
up experiments demonstrate that 4-hpr is anti-inflammatory in
the early hours after initial TPA treatment. We are evaluating
the possibility that 4-HPR stimulates apoptosis of
inflammatory cells. It appears from two separate experiments
that when fed on top of a soy- based semi-purified diet, NAC
at 1.5% and 3.0% of the diet stimulates the multiplicity of
these papillomas. This is most interesting because NAC is
usually inhibitory to the carcinogenic process- we have
identified a paradoxical activity of this antioxidant. This
phenomenon does not occur when NAC is fed in casein-based
diets. Thus, it appears there is an interaction between NAC
and some component(s) of the soy isolate (not occurring in the
casein-based diet) which cooperate to cause the increased
papilloma multiplicity. A second objective is to test the
hypothesis that the modulation of dietary antioxidants at two
distinctly different stages of pathogenesis will have opposite
effects on the eventual yield of malignant tumor formation. We
postulate that minimizing oxidative stress (by dietary
antioxidants) in the earliest stages (promotion) of tumor
pathogenesis will serve to functionally neutralize the
inflammatory component of tumor promotion, thereby eventually
translating to a decreased yield of malignant tumors. In
contrast, we anticipate that minimizing oxidative stress (thus
inhibiting apoptosis) specifically in the period when induced
lesions progress from preneoplasia through malignancy will
result in a selective advantage for the damaged cells and
eventually yield more malignancies. We therefore evaluated
this hypothesis using Tg.AC x p53 haploinsufficient mice
treated topically with B(a)P to induce skin carcinogenesis.
Compared to control diets, NAC feeding was associated with a
lower tumor burden (multiplicity) of tumors but stimulated it
stimulated their progression to malignancies. Finally, a
serendipitous observation from this skin cancer experiment was
that NAC feeding was associated with enhanced early deaths,
possibly from lymphomas. We have begun an in vivo
investigation to confirm and amplify this observation. An
analogous investigation in vitro shows that NAC
supplementation to mitogen treated splenocytes stimulates
proliferation and inhibits apoptosis. Thus we have identified
three contexts where the prototypic antioxidant exacerbated
tumor progression.
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会议论文
Mechanism(s) of Leukemogenesis in Genetically-Altered Mouse Models
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批准号:6432229
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Carcinogen inactivation of tumor suppressor genes in p53 haploinsufficient mice.
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批准号:6432252
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
CARCINOGEN INACTIVATION OF TUMOR SUPPRESSOR GENES IN P53 HAPLOINSUFFICIENT MICE.
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批准号:6289910
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Mechanism(s) Of Leukemogenesis In Genetically-altered Mo
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批准号:6837354
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Mechanism(s) Of Leukemogenesis In Disease Models
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批准号:7006469
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Carotenoid/Retinoid Modulation of Cellular Redox/Cancer
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批准号:6432261
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Genetic Susceptibility to Loss of Tumor Suppressor Gene Function
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批准号:7967960
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项目类别:
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资助金额:$8.97万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Genetic Susceptibility to Loss of Tumor Suppressor Gene
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批准号:7327256
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Carcinogen Inactivation Of Tumor Suppressor Genes In P53
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批准号:6542232
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Carcinogen Inactivation Of Tumor Suppressor Genes In P53
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批准号:6681846
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Genetic Susceptibility to Loss of Tumor Suppressor Gene
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批准号:7161820
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Carcinogen inactivation of tumor suppressor genes in p53 haploinsufficient mice.
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批准号:6106597
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
MECHANISM(S) OF LEUKEMOGENESIS IN GENETICALLY-ALTERED MOUSE MODELS
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批准号:6289887
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Leukemogenesis In Genetically-altered Models
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批准号:6546696
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Mechanism(s) Of Leukemogenesis In Genetically-altered Mo
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批准号:6681831
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Mechanism(s) of Leukemogenesis in Genetically-Altered Mouse Models
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批准号:6106571
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Carcinogen Inactivation Of Tumor Suppressor Genes In p53
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批准号:7006523
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Genetic Susceptibility to Loss of Tumor Suppressor Gene Function
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批准号:7734407
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项目类别:
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资助金额:$14.68万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Carotenoid/retinoid Modulation Of Cellular Redox Status
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批准号:6681901
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
Leukemogenesis In Genetically-altered Mouse Models
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批准号:7161813
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:JOHN EDGAR FRENCH
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依托单位:
海外基金