In wounded sugar beet (Beta vulgaris L.) tap-root, hexose accumulation correlates with the induction of a vacuolar invertase isoform.

Wounding of sugar beet tap-root causes an induction of invertase activity, which contributes to post-harvest sucrose losses. In this first comprehensive monitoring of wound-induced invertase mRNAs, proteins, enzyme activities, and tissue hexose concentrations, the VI isoform responsible for wound-induced hexose accumulation in mature tap-root could be identified.

Human developmental toxicity and mutagenesis.

A previously described SAR model of human developmental toxicity was analyzed further. The model shows a number of mechanistic similarities with SAR models of other toxicological phenomena (systemic toxicity, chromosomal and genomic effects). This implies that there are many targets associated with developmental effects. Surprisingly the analyses revealed no significant mechanistic overlap between developmental toxicity in humans and mutagenicity in Salmonella, a surrogate for the occurrence of point mutations. Our study indicates that this lack of similarity is likely the result of the pre-screening strategies which largely eliminate Salmonella mutagens from among the therapeutics introduced into human medicine.

Structural analysis of a group of phytoestrogens for the presence of a 2-D geometric descriptor associated with non-genotoxic carcinogens and some estrogens.

Analysis of a group of phytoestrogens indicates that the majority of these chemicals are devoid of a 6A distance descriptor biophore. This 6A biophore is associated with the carcinogenicity of a set of chemicals in the mouse subset of the Carcinogenic Potency Database assembled by Gold et al. The prevalence of non-DNA-reactive carcinogens and chemicals endowed with estrogenic activity included in the group of chemicals possessing 6A descriptor suggests that it describes a ligand binding site on an estrogen receptor. Evidence is presented that estrogens with and without the 6A biophore bind to alternate receptors or to similar receptors but with different affinities. Since the 6A biophore was identified based upon a carcinogenicity database, it is conceivable that binding to the putative receptor that recognizes this biophore is associated with carcinogenicity. Alternatively, estrogens devoid of this 6A biophore may be noncarcinogenic, suggesting that carcinogenicity and estrogenicity may be separate phenomena.

A dichotomy in the lipophilicity of natural estrogens, xenoestrogens, and phytoestrogens.

Using two independent analyses, it is demonstrated that natural (e.g., estradiol) and some xenoestrogens (e.g., methoxychlor metabolite) are characterized by a lipophilic region that is absent in nonestrogens as well as in phytoestrogens. It is suggested that this lipophilic region affects binding to specific receptors and may, in fact, differentiate harmful from beneficial estrogens.

The structural basis of the carcinogenic and mutagenic potentials of phytoalexins.

CASE, a structure-activity relational system, was used to predict the proportion of substances to be carcinogenic and mutagenic among plant pesticides (phytoalexins) and other natural products compared to that of randomly selected chemicals. There were no significant differences between phytoalexins and other natural products. On the other hand, the natural products, as a group, were predicted to be less mutagenic and carcinogenic than randomly selected chemicals. 37% of natural products are predicted to be rodent carcinogens.

Novel structural concepts in elucidating the potential genotoxicity and carcinogenicity of tetrandrine, a traditional herbal drug.

Tetrandrine, a widely used remedy, is predicted to be a 'genotoxic' carcinogen. This finding suggests that the usage of this substance in non-life-threatening situations should be evaluated.

Significant differences in the structural basis of the induction of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells.

The structural basis of the induction of sister chromatid exchanges (SCE) and chromosomal aberrations (Cvt) in Chinese hamster ovary cells was investigated by the CASE (Computer Automated Structure Evaluation) method, an artificial-intelligence-based system. Using the relevant National Toxicology Program data bases CASE identified a set of structural determinants responsible for the induction of SCE and another one for Cvt. A comparison between the structural determinants associated with SCE and Cvt revealed an overlap of only 22.6%, while the overlap between SCE and the determinants of mutagenicity in Salmonella is 54.5%. This indicates a) that the structural bases of the two phenomena differ and b) that it is likely that SCE, but not Cvt, involves a significant electrophilic/DNA-damaging component.

Airplane emissions: a source of mutagenic nitrated polycyclic aromatic hydrocarbons.

Organic solvent extracts from airplane emission particulates are mutagenic for Salmonella typhimurium strain TA98. Using Salmonella tester strains deficient in enzymes required for the bioactivation of various nitroarenes, the mutagenicity present in these emissions was ascribed to the presence of nitrated polycyclic aromatic hydrocarbons. Based on the known aircraft particulate emission rates at U.S. airports, and using 1-nitropyrene (1-NP) and 1,8-dinitropyrene (1,8-DNP) as surrogates, it is calculated that at a minimum 7 kg 1-NP and 20 g, 1,8-DNP are emitted daily at a typical U.S. airport.

Nitropyrenes: isolation, identificaton, and reduction of mutagenic impurities in carbon black and toners.

Extracts of selected xerographic toners and copies were found to be mutagenic in the Salmonella assay. The activity was independent of the xerographic hardware and process and was traced to nitropyrenes present as impurities in the carbon black, the toner colorant. Manufacturing process changes resulted in a substantial reduction of the nitropyrene content of the carbon black and thus in the mutagenicity of the corresponding toners. Nitropyrenes are potent frameshift mutagens, and possible mechanisms for their biological action are discussed.

A bactericidal activity of microsomal preparations.

Exposure of suspension of Salmonella typhimurium tester strains TA1535, TA1537 and TA98 to mouse hepatic post-mitochondrial supernatants (S9) resulted in appreciable loss of bacterial viability. This lethal activity was destroyed by heating at 56 degrees C for 30 min. The toxic component of the S9 has not been identified.

The E. coli Pol A-1 assay: a quantitative procedure for diffusible and non-diffusible chemicals.

A procedure is described for determining the preferential killing of DNA repair-deficient E. coli. Dilute suspensions of DNA repair-proficient and -deficient bacteria are exposed to a graded series of test chemical concentrations. Survivors are determined by enumeration on agar plates. An expression used to express preferential killing (or lack thereof) is shown to be dose-dependent and potentially useful for determining genotoxic potencies.

A new mutagenic and genotoxic response of the flame retardant tris(2,3-dibromopropyl)phosphate. Activation by singlet oxygen.

Illumination of tris (2,3-dibromopropyl)phosphate with visible light in the presence of riboflavin resulted in the formation of a stable product with greatly enhanced genetic and DNA-modifying activities. Because illumination of riboflavin results in the formation of short-lived singlet oxygen, it is assumed that the mutagenic and genotoxic chemical results from a reaction between the flame retardant and singlet oxygen. Since the polluted urban atmosphere is conducive to the generation of this species of oxygen, the present results may, therefore, be relevant to an assessment of the health hazard posed by such an environment.

Evaluation of the mutagenicity and DNA-modifying activity of carcinogens and noncarcinogens in microbial systems.

The mutagenicity of 99 chemicals was determined in a standard Salmonella typhimurium assay with the use of strains TA1535 and TA1538; the DNA-modifying capacity was determined with normal and DNA polymerase-deficient Escherichia coli strains. The following categories of chemicals were studied: alkylating agents (15); nitrosamines, hydrazines, and related substances (8); heterocyclics (10); aromatic amines (36); polycyclic aromatic hydrocarbons (11); amides, ureas, and acylating agents (7); antimetabolites (5); inorganics (4); and promoters (3). Of the substances studied, 21 were known noncarcinogens, 21 were ultimate carcinogens, and 45 were procarcinogens. Of the noncarcinogens, 35, 30, and 25% were positive in the Salmonella, E. coli, and both systems, respectively. All of the ultimate carcinogens were detectable as mutagens of DNA-modifying agents; 79, 100, and 79% gave positive tests in the Salmonella, E. coli, and both systems, respectively. Of the procarcinogens 72% were identifiable by these procedures: 52, 67, and 48% in the Salmonella, E. coli, and both assays, respectively. A tabulation of the combined data for ultimate carcinogens and procarcinogens indicates that 77% of the carcinogens gave positive results: 61, 74, and 59% in the Salmonella, E. coli, and both assays, respectively. We suggest that, for prescreening procedures with microbial assays, S. typhimurium strains TA98 and TA100 be included and the standard E. coli DNA polymerase-deficient assay be run in tandem with the Salmonella mutagenicity assay. When the standard E. coli DNA polymerase-deficient assay does not give interpretable results because of the lack of zones of growth inhibition, a modified assay with the use of liquid suspension should be performed.

Mutagenic activity of chemical carcinogens and related compounds in the intraperitoneal host-mediated assay.

The mutagenic activities of 79 carcinogens, noncarcinogens, and structurally related compounds toward Salmonella typhimurium strains TA1530, TA1535, and TA1538 and toward Saccharomyces cerevisiae D3 were investigated in the intraperitoneal host-mediated assay. Fewer than half of the carcinogens were mutagenic toward the Salmonella strains. The insensitivity of the system was most marked with the aromatic amine and polycyclic hydrocarbon procarcinogens. Under the test conditions, fewer than 10% of the carcinogens showed clear mutagenic activity toward S. cerevisiae D3. However, none of the noncarcinogens was significantly mutagenic toward either S. typhimurium or S. cerevisiae D3. Overall, the intraperitoneal host-mediated assay does not seem suitable for routine preliminary screening of large numbers of potential carcinogens. The median lethal doses to mice of 46 compounds were determined.

Phototherapy for neonatal hyperbilirubinemia--a potential environmental health hazard to newborn infants: a review.

Phototherapy has been shown to be an effective therapy for severe neonatal jaundice. However, because of its seemingly innocuous effect on normal babies, this therapeutic modality has been widely used to prevent jaundice in circumstances where it may be neither necessary nor beneficial. The present report summarizes results which indicate that phototherapy is endowed with DNA-modifying properties and has therefore the potential for inducing genetic and carcinogenic effects. These disconcerting findings concerning the long-term hazardous consequences of an accepted therapeutic procedure require that the unique physiologic and pharmacologic characteristics of the newborn populations be recognized when assessing the risks and benefits of phototherapy.