Individual Differences in DNA Repair Capacities in Man

Oesch, Franz; Aulmann, W.; Platt, Karl L.; Doerjer, Gerhard

doi:10.1007/978-3-642-71617-1_16

Cited by 46 publications

(21 citation statements)

References 4 publications

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“…Such wide differences are, in fact, predictable from clinical investigations on drug metabolism (23) and from studies of carcinogen metabolism among inbred strains of experimental animals (24). The interindividual variations observed here may not be related to the variations found in DNA repair among individuals (4,5). Our unpublished experiments have shown no significant repair of AF-and ABP-DNA adducts during 18-hr culture periods unless the PBLs were prestimulated with phytohemagglutinin.…”

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confidence: 51%

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Use of human peripheral blood lymphocytes to measure DNA binding capacity of chemical carcinogens.

Gupta

Earley

Sharma

1988

Proc. Natl. Acad. Sci. U.S.A.

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Although animal models have been used successfully to study metabolic activation and binding of carcinogens to DNA, only limited studies have been done in human systems. To circumvent the problems associated with the inaccessibility of human tissues and a lack of sensitive methods to detect DNA damage, we have investigated the capability of human peripheral blood lymphocytes in vitro to metabolize carcinogens to their DNA binding species by a 32P-labeled adduct assay. Freshly isolated lymphocytes were exposed at 37TC for 18 hr to 4-aminobiphenyl, 2

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confidence: 51%

“…In addition, the ability to repair DNA in human fibroblasts and leukocytes following exposure to some physical and chemical agents has been shown to vary widely (4,5). Whether individual variations in cancer risk and other diseases occur as a result of such mechanisms is less well known.…”

mentioning

confidence: 99%

Use of human peripheral blood lymphocytes to measure DNA binding capacity of chemical carcinogens.

Gupta

Earley

Sharma

1988

Proc. Natl. Acad. Sci. U.S.A.

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“…The profiles and DNA adduct levels can vary because of repair efficiency [Oesch et al, 1987]. Nevertheless, this type of approach should have significant relevance to future genetic toxicology studies.…”

Section: Discussionmentioning

confidence: 99%

Identification of genes responsive to BPDE treatment in HeLa cells using cDNA expression assays

Yu¹,

Ford²,

Glickman³

2000

Environ. Mol. Mutagen.

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“…PAH-DNA adducts can be repaired by a nucleotide excision pathway. A unimodal distribution of repair rates of benzo[a]pyrene diol-epoxide DNA adducts has been observed using human lymphocytes in vitro (23). The interindividual variation was substantially greater than the intraindividual variation, which suggests a role for inherited factors.…”

Section: Introductionmentioning

confidence: 92%

Pharmacogenetics: detecting sensitive populations.

Shields

1994

Environ Health Perspect

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Risk assessment models strive to predict risks to humans from toxic agents. Safety factors and assumptions are incorporated into these models to allow a margin of error. In the case of cancer, substantial evidence shows that the carcinogenic process is a multistage process driven by the interaction of exogenous carcinogenic exposures, genetic traits, and other endogenous factors. Current risk assessment models fail to consider genetic predispositions that make people more sensitive or resistant to exogenous exposures and endogenous processes. Several cytochrome P450 enzymes, responsible for metabolically activating carcinogens and medications, express wide interindividual variation whose genetic coding has now been identified as polymorphic and linked to cancer risk. For example, a restriction fragment-length polymorphism for cytochrome P4501A1, which metabolizes polycyclic aromatic hydrocarbons, and cytochrome P4502E1, which metabolizes N-nitrosamines and benzene, is linked to lung cancer risk. Cytochrome P4502D6, responsible for metabolizing many clinically important medications, also is linked to lung cancer risk. The frequency for each of these genetic polymorphisms vary among different ethnic and racial groups. In addition to inherited factors for the detection of sensitive populations, determining the biologically effective doses for carcinogenic exposures also should quantitatively and qualitatively enhance the risk assessment process. Levels of carcinogen-DNA adducts reflect the net effect of exposure, absorption, metabolic activation, detoxification, and DNA repair. These effects are genetically predetermined, inducibility notwithstanding. The combination of adduct and genotyping assays provide an assessment of risk that reflects recent exogenous exposure as well as one's lifetime ability to activate and detoxify carcinogens. -Environ Health Perspect 102(Suppl 1 1):81-87 (1994)

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Individual Differences in DNA Repair Capacities in Man

Cited by 46 publications

References 4 publications

Use of human peripheral blood lymphocytes to measure DNA binding capacity of chemical carcinogens.

Use of human peripheral blood lymphocytes to measure DNA binding capacity of chemical carcinogens.

Identification of genes responsive to BPDE treatment in HeLa cells using cDNA expression assays

Pharmacogenetics: detecting sensitive populations.

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