Evolutionary pattern and process within the Vertigo gouldii (Mollusca: Pulmonata, Pupillidae) group of minute North American land snails.

A phylogenetic analysis of 19 sibling taxa in the Vertigo gouldii group was conducted on 73 individuals sampled across North America using DNA sequence data of the mitochondrial genes cytochrome oxidase subunit 1 (CO1) and 16S ribosomal RNA (16S), and the internal transcribed spacer-2 of the nuclear ribosomal RNA (ITS-2) gene. The results of these analyses were found incongruent with previous taxonomic concepts used to define the V. gouldii group and its composite taxa that were based entirely on conchological features.

Human alpha class glutathione S-transferases: genetic polymorphism, expression, and susceptibility to disease.

The human alpha class glutathione S-transferases (GSTs) consist of 5 genes, hGSTA1-hGSTA5, and 7 pseudogenes on chromosome 6p12.1-6p12.2.

Expression of cytochromes P450 and glutathione S-transferases in human prostate, and the potential for activation of heterocyclic amine carcinogens via acetyl-coA-, PAPS- and ATP-dependent pathways.

Dietary factors appear to be involved in the high incidence of prostate cancer in "Westernized" countries, implicating dietary carcinogens such as heterocyclic amines (HAs) in the initiation of prostate carcinogenesis. We examined 24 human prostate samples with respect to their potential for activation and detoxification of HAs and the presence of DNA adducts formed in vivo. Cytochromes P450 1B1, 3A4 and 3A5 were expressed at low levels (<0.

Polymorphisms in genes related to oxidative stress (MPO, MnSOD, CAT) and survival after treatment for breast cancer.

The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H(2)O(2), with catalase neutralizing H(2)O(2) and myeloperoxidase converting H(2)O(2) to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified.

Potential chemoprotective effects of the coffee components kahweol and cafestol palmitates via modification of hepatic N-acetyltransferase and glutathione S-transferase activities.

Coffee drinking has been associated with reduced incidence of colorectal cancer, possibly via chemoprotection/modification of the metabolism of dietary heterocyclic amine carcinogens such as 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) by kahweol and cafestol palmitates (K/C), two components of unfiltered coffee. Using the PhIP-exposed male Fisher F344 rat as a model, K/C have been shown to reduce colonic PhIP-DNA adducts by > 50%. We have used the male F344 rat to investigate the effects of dietary K/C (0.

Lack of association between Caucasian lung cancer risk and O6-methylguanine-DNA methyltransferase-codon 178 genetic polymorphism.

The formation of DNA adducts is thought to be a critical step for the induction of chemically induced cancer. O(6)-Methylguanine-DNA methyltransferase (MGMT) is a ubiquitously expressed enzyme that repairs DNA adducts formed by alkylating carcinogens. Thus, genetic polymorphisms of the MGMT that could result in differences in MGMT activity are potential risk factors for cancer.

Human glutathione S-transferase A2 polymorphisms: variant expression, distribution in prostate cancer cases/controls and a novel form.

Variability of expression of the major glutathione S-transferases (GSTs) of liver, GSTA1 and GSTA2, is thought to affect the efficiency of detoxification of xenobiotics, including chemical carcinogens. Polymorphism of the GSTA1 regulatory sequence determines some of the variation of hepatic GSTA1 expression, but the polymorphisms in GSTA2 (exons 5 and 7) were not thought to affect GSTA2 activity. By examining GST protein expression for a set of human liver and pancreas samples (coupled with a cloning/polymerase chain reaction-restriction fragment length polymorphism strategy), we identified a novel substitution Pro110Ser (328C>T) and the corresponding novel variant GSTA2*E (Ser110Ser112Lys196Glu210), and confirmed the presence of variants GSTA2*A (Pro110Ser112Lys196Glu210), GSTA2*B (Pro110Ser112Lys196Ala210) and GSTA2*C (Pro110Thr112Lys196Glu210).

Gene and protein characterization of the human glutathione S-transferase kappa and evidence for a peroxisomal localization.

Kappa class glutathione S-transferase (GST) cDNA sequences have been identified in rat, mouse, and human. In the present study, we determined the structure and chromosomal location of the human GST Kappa 1 (hGSTK1) gene, characterized the protein, and demonstrated its subcellular localization. The human gene spans approximately 5 kb, has 8 exons, and maps onto chromosome 7q34.

Detoxification of electrophilic compounds by glutathione S-transferase catalysis: determinants of individual response to chemical carcinogens and chemotherapeutic drugs?

The glutathione S-transferases (GSTs) catalyze the GSH-dependent detoxification of reactive electrophiles such as genotoxic chemical carcinogens and cytotoxic chemotherapeutic agents. Allelic polymorphism in the GSTs has been used to investigate the hypothesis that GSTs are involved in susceptibility to human cancers. Such studies have resulted in low penetrance, high prevalence associations between cancer risk and GST polymorphisms.

Association between a glutathione S-transferase A1 promoter polymorphism and survival after breast cancer treatment.

Glutathione S-transferase (GST) enzymes detoxify chemotherapeutic drugs, and several studies have reported differences in survival for cancer patients who have variant genotypes for GSTP1, GSTM1 or GSTT1 enzymes. A recently described polymorphism alters hepatic expression of GSTA1, a GST with high activity in glutathione conjugation of metabolites of cyclophosphamide (CP). To consider the possible influence of the reduced-expression GSTA1*B allele on cancer patient survival, we have conducted a pilot study of breast cancer patients treated with CP-containing combination chemotherapy.

Novel markers of susceptibility to carcinogens in diet: associations with colorectal cancer.

Red meats cooked at high temperatures generate mutagenic heterocyclic amines, which undergo metabolic activation by hepatic cytochrome P450 1A2 and N-acetyltransferase-2. A primary detoxification pathway involves glutathione S-transferase A1 (GSTA1), which catalyzes the reduction of the carcinogenic N-acetoxy derivative back to the parent amine. Recently, we described a polymorphism in the GSTA1 proximal promoter; the variant (GSTA1*B) allele significantly lowers enzyme expression.

Effects of the ADH3, CYP2E1, and GSTP1 genetic polymorphisms on their expressions in Caucasian lung tissue.

Individual differences in lung cancer susceptibility should be considered for effective lung cancer prevention. We investigated the CYP2E1, ADH3, and GSTP1 genetic polymorphisms that biotransform xenobiotic carcinogens, and variations of their enzyme activity in Caucasian lung tissues (N=28), and found a variant distribution in pulmonary ADH and CYP2E1 activity. The ADH3*1/*1 subjects (N=8) showed significantly higher ADH activity than ADH3*2/*2 (N=3) subjects (P<0.

Analysis of total meat intake and exposure to individual heterocyclic amines in a case-control study of colorectal cancer: contribution of metabolic variation to risk.

A case-control study of colorectal cancer, consisting of 157 cases and 380 controls matched by sex, ethnicity, decade of age and county of residence was performed to explore the associations between environmental exposure, metabolic polymorphisms and cancer risk. Participants were required to provide a blood sample, undergo caffeine phenotyping and complete an in-person interview that evaluated meat consumption, cooking methods and degree of doneness. A color atlas of foods cooked to different degrees of doneness was used to estimate food preparation techniques and food models were used to estimate serving portion sizes.

Interindividual variation and organ-specific patterns of glutathione S-transferase alpha, mu, and pi expression in gastrointestinal tract mucosa of normal individuals.

Glutathione S-transferase (GST) protein in gastrointestinal (GI) tracts of 16 organ donors, from whom all or substantial portions of the GI tract (stomach-colon) were available, was quantitated by HPLC and examined for interindividual variability/consistency of organ-specific patterns of expression. GSTP1, GSTA1, and GSTA2 were major components, and GSTM1 and GSTM3 were minor components. Consistent patterns of organ-specific expression were evident despite a high degree of interindividual variation of expression.

The human glutathione transferase alpha locus: genomic organization of the gene cluster and functional characterization of the genetic polymorphism in the hGSTA1 promoter.

By searching the human genome sequence database with human hGSTA1 and hGSTA4 cDNA sequences, we identified three PAC and one BAC clones covering more than 400 kilobases and containing the entire GST alpha gene cluster. The cluster consists of five genes: hGSTA1, hGSTA2, hGSTA3, hGSTA4 and hGSTA5, and seven pseudogenes that are distinguished as such by single-base and/or complete exon deletions. Using gene-specific probes we demonstrated that hGSTA1, hGSTA2 and hGSTA4 mRNAs are widely expressed in human tissues, whereas hGSTA3 mRNA appears to be a rare message subject to splicing defects.