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Several lines of evidence indicate that diet and dietary behaviors can contribute to human cancer risk. One way that this occurs is through the ingestion of food mutagens. Sporadic cancers result from gene-environment interactions where the environment includes endogenous and exogenous exposures. In this article, we define environment as dietary exposures in the context of gene-environment interactions. Food mutagens cause different types of DNA damage: nucleotide alterations and gross chromosomal aberrations. Most mutagens begin their action at the DNA level by forming carcinogen-DNA adducts, which result from the covalent binding of a carcinogen or part of a carcinogen to a nucleotide. However, the effect of food mutagens in carcinogenesis can be modified by heritable traits, namely, low-penetrant genes that affect mutagen exposure of DNA through metabolic activation and detoxification or cellular responses to DNA damage through DNA repair mechanisms or cell death. There are some clearly identified (e.g., aflatoxin) and suspected (e.g., N-nitrosamines, polycyclic aromatic hydrocarbons or heterocyclic amines) food mutagens. The target organs for these agents are numerous, but there is target-organ specificity for each. Mutagenesis, however, is not the only pathway that links dietary exposures and cancers. There is growing evidence that epigenetic factors, including changes in the DNA methylation pattern, are causing cancer and can be modified by dietary components. Also DNA damage may be indirect by triggering oxidative DNA damage. When considering the human diet, it should be recognized that foods contain both mutagens and components that decrease cancer risk such as antioxidants. Thus nutritionally related cancers ultimately develop from an imbalance of carcinogenesis and anticarcinogenesis. The best way to assess nutritional risks is through biomarkers, but there is no single biomarker that has been sufficiently validated. Although panels of biomarkers would be the most appropriate, their use as a reflection of target-organ risk remains to be determined. Also even when new biomarkers are developed, their application in target organs is problematic because tissues are not readily available. For now most biomarkers are used in surrogate tissues (e.g., blood, urine, oral cavity cells) that presumably reflect biological effects in target organs. This article reviews the role of food mutagens in mutagenesis and carcinogenesis and how their effects are modified by heritable traits and discusses how to identify and evaluate the effects of food mutagens. KEY WORDS: * biomarkers * diet assessment, epidemiology * mutagens * nutrition

Research has been conducted on chromiumchromium(VI) mutagenicity. The study of mutational spectrum and the role of oxidative damage and chromium-DNA adducts in chromium(VI) mutagenicity activated by biologically relevant concentrations of ascorbate has been carried out, and the differences in genotoxic and mutagenic responses to chromium-DNA adducts between bacterial and human cells have been investigated and discussed.

Research has been conducted on mitochondrial adenine nucleotide carrier. The study of the human mitochondrial adenine nucleotide carrier coding gene expression in yeast Saccharomyces cerevisiae triple mutant has been carried out, and the ADP/ATP exchange kinetics of the human carriers has been analyzed and discussed.

Research has been conducted on aminoacyl-tRNA synthetases. The functions of human tyrosyl-tRNA synthetase beond aminoacylation have been investigated via the use of yeast tyrosyl-tRNA synthetase which lacks cytokine activity, and the results demonstrate that mutant yeast tyrosyl-tRNA synthetase has gained cytokine function.

Research has been conducted on mammalian iron-binding proteins lactoferrin and transferrin. The functional and structural differences between these proteins and the factors modulating the interactions in disyline trigger region have been investigated via mutation of Arg 210 to Gly, Glu and Leu in the recombinant N-lobe of human lactoferrin, and the results are reported.

Research has been conducted on Rhodobacter sphaeroides ribulose 1,5-bisphosphate carboxylase-oxygenase deletion strain. The increase of the gene transcription of Calvin-Benson-Bassham cycle has indicated the existence of a potential physiological effector enhancing the ability of the positive transcription activator to mediate Calvin-Benson-Bassham pathway intermediate.

Research has been conducted on hyfA-lacZ transcriptional fusion in Escherichia coli. The study of this fusion carried out in investigating hyf expression under different growing conditions and various mutant backgrounds is described.

Research has been conducted on Rhodobacter sphaeroides prrA mutant. Experiments demonstrate that this mutant can be involved in dark chemoautotrophic growth in H (sub)2- CO (sub)2 -O (sub)2 atmosphere.

Research has been conducted on Streptomyces clavuligerus ccaR::aph strain disrupted in the regulatory gene ccaR. The formation of holomycin and holomycin synthase activities in S. clavuligerus mutants with disruption in various genes involved in clavulanic acid production is described.

Research has been conducted on Pseudomonas aeruginosa transposon insertion mutants. Results demonstrate that Pseudomonas quinolone signal levels correlate with autolysis and that the natural populations of P. aeruginosa is in ballance between survival and persistence of certain groups of populations.

Research has been conducted on Bacillus thuringiensis mutant. The characterization of this mutant which is defective in flagellum gilament assembly, in swimming and swarming motility and in produvtion of hemolysin BL has been carried out and is described.

Research has been conducted on Streptococcus mutans stress responses. The role of clp genes in these stress responses has been identified, and the results indicate that the increased production of GroESL and DbaK in clpP mutant suggests that the cells are stressed due to the denatured protein accumulation.

Research has been conducted on phage-sensitive Lactococcus lactis strains constructed via the use of natural plasmids coding for phase-resistance into phage-sensitive strains. Results demonstrate that the use of these phase-resistance cultures is affected by emerging phage mutants capable of overcoming antiviral systems.

Research has been conducted on gonococcal transferrin binding protein A and TonB. The ability of generated TonB mutants to interact with gonococcal transferrin binding protein A and the effect of characterized TonB-box mutation in gonococcal transferrin binding protein A on gonococcal transferrin binding protein A-TonB interaction have been investigated and discussed.

Research has been conducted on Bacillus subtilis PrpC serine-threonine phosphatase and PrkC kinase. The effects of loss-of-function muitations within prpC and prkC and the role of PrpC and PrkC in controlling different stationary-phase processes have been investigated and discussed.

Research has been conducted on Borrelia burgdorferi, Lyme disease causative agent. The up-regulation of GroEL protein and groEL mRNA transcript carried out in bacterium's gyrB mutants is described.

Research has been conducted on Caulobacter crescentus sensor kinase which is important for cell division. The sequences within this kinase required for polar localization have been identified via the study of the mutagenized sequences' ability to direct green fluorescent protein localization, and the details are reported.

In mammals, the adhesion and fusion of the palatal shelves are essential mechanisms in the development of the secondary palate. Failure of any of these processes leads to the formation of cleft palate. The mechanisms underlying palatal shelf adhesion are poorly understood, although the presence of filopodia on the apical surfaces of the superficial medial edge epithelial (MEE) cells seems to play an important role in the adhesion of the opposing MEE. We demonstrate here the appearance of chondroitin sulphate proteoglycan (CSPG) on the apical surface of MEE cells only immediately prior to contact between the palatal shelves. This apical CSPG has a functional role in palatal shelf adhesion, as either the alteration of CSPG synthesis by [beta]-D-Xyloside or its specific digestion by chondroitinase AC strikingly alters the in vitro adhesion of palatal shelves. We also demonstrate the absence of this apical CSPG in the clefted palates of transforming growth factor beta 3 (TGF-[[beta].sub.3]) null mutant mice, and its induction, together with palatal shelf adhesion, when TGF-[[beta].sub.3] is added to TGF-[[beta].sub.3] null mutant palatal shelves in culture. When chick palatal shelves (that do not adhere in vivo nor express TGF-[[beta].sub.3], nor CSPG in the MEE) are cultured in vitro, they do not express CSPG and partially adhere, but when TGF-[[beta].sub.3] is added to the media, they express CSPG and their adhesion increases strikingly. We therefore conclude that the expression of CSPG on the apical surface of MEE cells is a key factor in palatal shelf adhesion and that this expression is regulated by TGF-[[beta].sub.3]. Key Words: palate fusion; chondroitin sulphate proteoglycan; cleft palate; TGF-[[beta].sub.3] null mutant mouse; chick.

Efficient bypass of an abasic (AP) site by the combined action of yeast DNA polymerases delta and zeta has been shown. From the pattern of mutations brought on by AP sites in yeast, it appears likely that in vivo A nucleotide is the residue inserted most often opposite AP sites. Biochemical studies make it appear that Pol delta usually inserts an A opposite the AP site. Efficient bypass of the lesion occurs when Pol delta and Pol zeta are together. Steady-state kinetic analyses show Pol zeta to be very inefficient in putting nucleotides opposite the PA site.

Research has been conducted on the eosinophils peroxidase. The possibility that the hypobromous acid generated by this peroxidase can oxidize nucleic acids has been investigated.

Results show that interaction between 8-oxodGTP and aspergine 279 at the DNA polymerase site probably alters conformation of the 8-oxodGTP resulting in its misincorporation by the polymerase.

The crystal structure of the mutagenic protein UmuD of Escherichia coli at 2.5 angstrom resolution reveals globular heads folded in a rare beta-structure that cohere to form dimer molecules. The extended amino-acid tail congregate to form crystallized filaments. UmuD filament forms a scaffold on the RecA-DNA filament that places UmuC efficiently for interaction with DNA polymerase III holoenzyme. Analysis of the structure indicates that UmuD undergoes self-cleavage reactions during the global SOS response.

Research delineates a pathway for the elimination of the purine base N-6-hydroxylaminopurine (HAP) from purine pools, deoxynucleotide triphosphate pools, and from DNA. The proposed model consists of enzymes to detoxify HAP, remove noncanonical deoxyribonucleotide phosphates, and HAP removal from DNA.

RNA viruses evolve rapidly. One source of this ability to rapidly change is the apparently high mutation frequency in RNA virus populations. A high mutation frequency is a central tenet of the quasispecies theory. A corollary of the quasispecies theory postulates that, given their high mutation frequency, animal RNA viruses may be susceptible to error catastrophe, where they undergo a sharp drop in viability after a modest increase in mutation frequency. We recently showed that the important broad-spectrum antiviral drug ribavirin (currently used to treat hepatitis C virus infections, among others) is an RNA virus mutagen, and we proposed that ribavirin's antiviral effect is by forcing RNA viruses into error catastrophe. However, a direct demonstration of error catastrophe has not been made for ribavirin or any RNA virus mutagen. Here we describe a direct demonstration of error catastrophe by using ribavirin as the mutagen and poliovirus as a model RNA virus. We demonstrate that ribavirin's antiviral activity is exerted directly through lethal mutagenesis of the viral genetic material. A 99.3% loss in viral genome infectivity is observed after a single round of virus infection in ribavirin concentrations sufficient to cause a 9.7-fold increase in mutagenesis. Compiling data on both the mutation levels and the specific infectivities of poliovirus genomes produced in the presence of ribavirin, we have constructed a graph of error catastrophe showing that normal poliovirus indeed exists at the edge of viability. These data suggest that RNA virus mutagens may represent a promising new class of antiviral drugs.

The hepatoprotective and antimutagenic effects of the rosemary essential oil and the ethanolic extract were investigated using carbon tetrachloride and cyclophosphamide as hepatotoxic and mutagenic compounds, respectively. Our results revealed that i.g. administration of the rosemary ethanolic extract (0.15 g/100 g BW) to rats for 3 weeks produced the most pronounced hepatoprotective effect compared to silymarin (reference compound) due to the amelioration of most of the studied serum and liver parameters and confirmed by histopathological examination of the liver tissue. Pretreatment of mice for 7 days with the rosemary essential oil (1.1 mg/g BW) followed by i.p. injection with cyclophosphamide reduced significantly the induced mitodepression in the bone marrow cells of the animals. The potential hepatoprotective and antimutagenic activities of the rosemary ethanolic extract and essential oil, respectively, are attributed to the presence of a relatively high percentage of phenolic compounds with high antioxidant activity (according to our chemical studies)., Introduction Humans are constantly exposed to a complex blend of toxicants and carcinogens as detoxification of xenobiotic and toxic substances is an important hepatic function, in the course of which [...]