Application Of Benzo Research Articles

Potential Application of Benzo(a)Pyrene-Associated Adducts (Globin or Lipid) as Blood Biomarkers for Target Organ Exposure and Human Risk Assessment

In order to investigate the potential application of blood biomarkers as surrogate indicators of carcinogen–adduct formation in target-specific tissues, temporal formation of benzo[a]pyrene (BaP)-associated DNA adducts, protein adducts, or lipid damage in target tissues such as lung, liver, and kidney was compared with globin adduct formation or plasma lipid damage in blood after continuous intraperitoneal (ip) injection of [3H]BaP into female ICR mice for 7 d. Following treatment with [3H]BaP, formation of [3H]BaP–DNA or –protein adducts in lung, liver, and kidney increased linearly, and persisted thereafter. This finding was similar to the observed effects on globin adduct formation and plasma lipid damage in blood. The lungs contained a higher level of DNA adducts than liver or kidneys during the treatment period. Further, the rate of cumulative adduct formation in lung was markedly greater than that in liver. Treatment with a single dose of [3H]BaP indicated that BaP–globin adduct formation and BaP–lipid damage in blood reached a peak 48 h after treatment. Overall, globin adduct formation and lipid damage in blood were significantly correlated with DNA adduct formation in the target tissues. These data suggest that peripheral blood biomarkers, such as BaP–globin adduct formation or BaP–lipid damage, may be useful for prediction of target tissue-specific DNA adduct formation, and for risk assessment after exposure.

Application of benzo[a]phenoxazinium chlorides in antimicrobial photodynamic therapy of Candida albicans biofilms

The use of Antimicrobial Photodynamic Therapy (APDT) as a new approach to treat localized Candida infections is an emerging and promising field nowadays. The aim of this study was to verify the efficacy of photodynamic therapy using two new benzo[a]phenoxazinium photosensitizers against Candida albicans biofilms: N-(5-(3-hydroxypropylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSc) and N-(5-(11-hydroxyundecylamino)-10-methyl-9H-benzo[a]phenoxazin-9-ylidene)ethanaminium chloride (FSd). The photodynamic activity of dyes against C. albicans biofilms was evaluated by incubating biofilms with dyes in the range of 100–300μM for 3 or 18h followed by illumination at 12 or 36Jcm−2, using a xenon arc lamp (600±2nm). A total photoinactivation of C. albicans biofilm cells was achieved using 300μM of FSc with 18h of incubation, followed by illumination at 36Jcm−2. Contrarily, FSd had insignificant effect on biofilms inactivation by APDT. The higher uptake of FSc than FSd dye by biofilms during the dark incubation may explain the greater photodynamic effectiveness achieved with FSc. The results obtained stresses out the FSc-mediated APDT potential use to treat C. albicans infections.

Induced suppression of soft rot disease in tobacco by combined application of Bacillus subtilis strain B4 and chemical elicitor BTH

In this study, the utility of the combined application of Benzo-(1,2,3)-thidiazole-7-carbothioic acid S-methyl ester (BTH), a systemic acquired resistance (SAR) inducer, and the plant growth-promoting rhizobacteria (PGPR), Bacillus subtilis strain B4 (B4), was investigated for the suppression of soft rot disease caused by Pectobacterium carotovorum SCC1 (SCC1) in tobacco seedlings. Soft rot disease was completely suppressed in tobacco with combined application of B4 strain and 0.1 mM BTH when compared to individual application upon pathogen challenge. In addition, the population of bacterial cells of B4 strain was found to be greater when cultured in growth media in the presence of BTH, compared to the growth of B4 strain in the absence of BTH. Spectrophotometer analysis revealed that there was an increased broad range of compounds in the culture filtrate of B4 strain when grown with BTH, compared to the culture filtrate of B4 strain alone. The combined application of B4 strain and 0.1 mM BTH induced the increased expression of PR1a::GUS on tobacco and elicited systemic resistance against SCC1 when compared to individual application. However, there was low expression of PR1a::GUS in the water-treated control. Hence, the integrated use of BTH and B4 strain might be one of the strategies for biological control of soft rot disease through induced systemic resistance (ISR) in tobacco plants.

Salicylic Acid Regulates Basal Resistance to Fusarium Head Blight in Wheat

Fusarium head blight (FHB) is a destructive disease of cereal crops such as wheat and barley. Previously, expression in wheat of the Arabidopsis NPR1 gene (AtNPR1), which encodes a key regulator of salicylic acid (SA) signaling, was shown to reduce severity of FHB caused by Fusarium graminearum. It was hypothesized that SA signaling contributes to wheat defense against F. graminearum. Here, we show that increased accumulation of SA in fungus-infected spikes correlated with elevated expression of the SA-inducible pathogenesis-related 1 (PR1) gene and FHB resistance. In addition, FHB severity and mycotoxin accumulation were curtailed in wheat plants treated with SA and in AtNPR1 wheat, which is hyper-responsive to SA. In support of a critical role for SA in basal resistance to FHB, disease severity was higher in wheat expressing the NahG-encoded salicylate hydroxylase, which metabolizes SA. The FHB-promoting effect of NahG was overcome by application of benzo (1,2,3), thiadiazole-7 carbothioic acid S-methyl ester, a synthetic functional analog of SA, thus confirming an important role for SA signaling in basal resistance to FHB. We further demonstrate that jasmonate signaling has a dichotomous role in wheat interaction with F. graminearum, constraining activation of SA signaling during early stages of infection and promoting resistance during the later stages of infection.

The Effects of a Powder of the Fruiting Body of Commercial Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (W.Curt.:Fr.) P.Karts.,] on Hypercholesterolemic Rat Skin, Applied With a Topical Application of Benzo(a)pyrene

The Effects of a Powder of the Fruiting Body of Commercial Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (W.Curt.:Fr.) P.Karts.,] on Hypercholesterolemic Rat Skin, Applied With a Topical Application of Benzo(a)pyrene

Benzo[ b]thiophen-3(2 H)-one 1,1-dioxide—a versatile reagent in the synthesis of spiroheterocycles

New applications of benzo[ b]thiophen-3(2 H)-one 1,1-dioxide have been investigated. The synthesis of a new heterocyclic system 3 H,2′ H-spiro[benzo[ b]thieno[3,2- b]pyridine-3,2′-benzo[ b]thiophene] is described and a mechanism for the cyclisation is proposed.

Benzo[b]naphthyridines

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Application of benzo(a)pyrene and coal tar tumor dose-response data to a modified benchmark dose method of guideline development.

Assessment of cancer risk from exposure to polycyclic aromatic hydrocarbons (PAHs) has been traditionally conducted by applying the conservative linearized multistage (LMS) model to animal tumor data for benzo(a)pyrene (BaP), considered the most potent carcinogen in PAH mixtures. Because it has been argued that LMS use of 95% lower confidence limits on dose is unnecessarily conservative, that assumptions of low-dose linearity to zero in the dose response imply clear mechanistic understanding, and that “acceptable” cancer risk rests on a policy decision, an alternative cancer risk assessment approach has been developed. Based in part on the emerging benchmark dose (BMD) method, the modified BMD method we used involves applying a suite of conventional mathematical models to tumor dose–response data. This permits derivation of the average dose corresponding to 5% extra tumor incidence (BMD0.05) to which a number of modifying factors are applied to achieve a guideline dose, that is, a daily dose considered safe for human lifetime exposure. Application of the modified BMD method to recent forestomach tumor data from BaP ingestion studies in mice suggests a guideline dose of 0.08 μg/kg/day. Based on this and an understanding of dietary BaP, and considering that BaP is a common contaminant in soil and therefore poses human health risk via soil ingestion, we propose a BaP soil guideline value of 5 ppm (milligrams per kilogram). Mouse tumor data from ingestion of coal tar mixtures containing PAHs and BaP show that lung and not forestomach tumors are most prevalent and that BaP content cannot explain the lung tumors. This calls into question the common use of toxicity equivalence factors based on BaP for assessing risk from complex PAH mixtures. Emerging data point to another PAH compound—7H-benzo(c)fluorene—as the possible lung tumorigen.

Evidence for Systemic, Cross-resistance in White Clover ( Trifolium repens ) and Annual Medic ( Medicago truncatula var truncatula ) Induced by Biological and Chemical Agents

Soil-based growth cabinet and greenhouse experiments were designed to determine whether a resistance response previously noted in Trifolium repens to the clover cyst nematode Heterodera trifolii was systemic and also effective against a pest from a different taxon. Root applications of benzo(1,2,3)thiadiazole-7-carbothioic acid-S-methyl ester (BTH) or a Pseudomonas -like bacterial strain P29 to white clover seedlings induced resistance to the blue-green aphid, Acyrthosiphon kondoi . A similar response was observed in the annual medic, Medicago truncatula var truncatula . Estimation of lignin and callose content of whole plants at the termination of the bioassay showed no differences between treated and control plants. The significance of these findings is discussed.

ChemInform Abstract: Recent Advances in the Synthesis and Applications of Benzo[b]thiophenes

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Recent Advances in the Synthesis and Applications of Benzo[b]thiophenes

Recent developments in the application and synthesis of benzo[b]thiophenes are reviewed, with an emphasis on various cyclization methodologies leading to the heterocyclic core structure.

Application of Benzo[h]naphthyridinium‐N‐carboethoxymethylides as 1,3‐dipoles

Application of Benzo[h]naphthyridinium‐N‐carboethoxymethylides as 1,3‐dipoles

Glucocorticoids and benzo(a)pyrene had opposing effects on EGF receptor binding.

The potent tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and related phorbol ester tumour promoters, act by binding to specific high affinity receptors on the cell surface and this leads to changes in cell membrane structure and function, as well as highly pleiotropic effects on gene expression1–3. The ability of the phorbol ester tumour promoters4–7, and of a recently discovered tumour promoter, teleocidin8, to induce inhibition of the binding of epidermal growth factor (EGF) to its cell-surface receptors provides a convenient marker for the membrane effects of these tumour promoters. The fact that repeated applications of benzo(a)pyrene (BP) alone to mouse skin will elicit tumours suggests that it can function as both an initiator and a promoter9,10. Thus, in addition to its genotoxic effects, BP might induce membrane effects that resemble those seen with tumour promoters. Indeed, we have found that BP and certain other polycyclic aromatic hydrocarbons (PAHs) are potent inhibitors of EGF-receptor binding in the mouse embryo fibroblast cell line C3H10T½ (ref. 11). As glucocorticoids can inhibit PAH carcinogenesis12,13 and specifically inhibit tumour promotion on mouse skin14,15, we have also examined their effects on EGF receptors. We report here that glucocorticoids alone induce an increase in EGF-receptor binding in C3H10T½ cells and that pretreatment of the cells with a glucocorticoid opposes the inhibitory effects of both TPA and BP. Thus glucocorticoids may inhibit the carcinogenic process by inducing membrane effects that are reciprocal to those induced by carcinogens and tumour promoters.

The basement membrane in experimentally induced atypias and carcinoma of the uterine cervix in mice

Basement membrane-specific antigens of the squamous epithelium of the uterine cervix were investigated in 19 normal mice, in 7 mice with cervical atypia and in 3 mice with invasive carcinoma. Cervical atypia and carcinoma were induced by local application of benzo(a)pyrene. Basement membrane-specific antigens were demonstrated by immunofluorescence with sera from patients with bullous pemphigoid. Both normal squamous cervical epithelium and atypical cervical epithelium showed the presence of a continuous, clearly delineated basement membrane. Clusters of invasive squamous carcinoma were also surrounded by a fluorescent basement membrane which, however, appear fragmented or discontinuous. The results suggest that the ability of cervical squamous cells to secrete basement membrane antigens is not completely lost during carcinogenesis, thus substantiating our previous observations in the cervix of human subjects.

Action of 7,8-benzoflavone on incidence of skin tumors induced by polycyclic hydrocarbons

Tumors were induced in CBA mice or (C57BL×CBA)F1 hybrids by application of benzo-(a) pyrene (BP), 6-methyl-BP, 6-formyl-BP, or 7,12-dimethylbenz (a) anthracene (DMBA) to the dorsal skin. If 7,8-benzoflavone (BF) was mixed with the above compounds it reduced the carcinogenic action of the methyl-substituted hydrocarbons (DMBA and 6-methyl-BP) but did not affect the carcinogenic action of BP itself or of 6-formyl-BP. The inhibitory action of BF on carcinogenesis induced by methyl-substituted hydrocarbons is due, it can tentatively be suggested, to inhibition of oxidation of the methyl group.

Lack of effect of trichloropropene oxide on benzo(a)pyrene tumor-initiating activity on mouse skin

The potent epoxide hydratase (EH) inhibitor, 1,1,1,-trichloro- 2,3-propene oxide (TCPO), did not enhance the tumor-initiating ability of benzo(a)pyrene (BP) when applied simultaneously with BP in a two-stage system of tumorigenesis in male Swiss mice. BP ( 0.1 μmole) with or without TCPO ( 2 μmole) was applied either once (day 1 or twice 1 and 3 to the skin of the backs of mice shaved 24 hr before; thereafter the mice were given weekly applications of croton oil ( 50 μl1% in acetone per mouse for 50 weeks). Skin tumors started to appear 15 weeks after initiation of the mice, and at the same time in all groups. The experiment was terminated 50 weeks after application of carcinogen. The skin microsomal epoxide hydratase ( 48–52 pmole BP- 4,5 diol/min/mg) was inhibited 3 hr after application of BP alone or BP plus TCPO. No inhibition was observed in microsomes isolated 16 or 24 hr after application of carcinogen or carcinogen plus epoxide hydratase inhibitor. TCPO has no in vitro effect on the 3H -BP binding to epidermal DNA 24 hr after application of benzo(a)pyrene. Rapid trapping of TCPO by intracellular glutathione and/or nucleophiles would explain this absence of effect, which contradicts the results of D. L. Berry and other ( J. Nat. Cancer Inst. Vol. 58, No. 4, 1051–1055, 1977).

Rate of Cell Division in Atypias and Invasive Carcinoma of the Uterine Cervix of the Mouse2

The rate of cell division during a 6-hour period was determined in cervical epithelia from 64 normal mice, 26 mice with cervical atypias, and 8 mice with invasive carcinomas. Cervical atypias and carcinomas were induced by local application of benzo[a]pyrene (BP), and mitosis was arrested with colchicine. Values for the ratio of dividing basal cells to total dividing cells and for the rates of basal cell division for the 6-hour period were both significantly greater in normal epithelia than in atypias, and these values for atypias were greater than those for invasive carcinomas. The differences were not estrous cycle-dependent. There was no evidence that the mechanism of host invasion by squamous tumor cells was due to an increased number of cells in mitoses. The occurrence of areas with mitotic activity suggested the existence of focally distributed and probably alternating, synchronous cell production in normal cervical epithelium. This property was apparently not altered by topical BP application or by carcinogenesis.

Genetic differences in the induction of aryl hydrocarbon hydroxylase and benzo(a)pyrene carcinogenesis in C3H/He and DBA/2 strains of mice.

The effects of 3-methylcholanthrene and 5,6- and 7,8-benzoflavones on aryl hydrocarbon (benzo[a]pyrene) hydroxylase in the liver, small intestine, lung, and skin tissues from C3H/He and DBA/2 strains of mice under the controlled lighting conditions were examined. Apparent differences were observed in the inducibility of the hepatic enzyme by the inducers between the two strains of mice, showing that the enzyme in the C3H/He mice is inducible but not in the DBA/2 mice. Comparison of the results on the enzyme induction by 3-methylcholanthrene in the liver among the parent, intercrossed, and backcrossed mice suggested that the inducibility may be inherited as a single autosomal dominant trait. However, different genetic responses to 3-methylcholanthrene and benzoflavones in the enzyme of small intestine might be considered, because a discrepancy in the inducibility of the enzyme between the liver and the small intestine from the identical mice was demonstrated when the progeny of F2 and (DBA/2 times F1) backcross were used. On the other hand, no apparent difference was found in the inducibility of the enzyme in the lung and skin between the C3H/He and the DBA/2 mice. It is assumed that the genetic regulation of the induction of aryl hydrocarbon hydroxylase was separately controlled in the respective tissues from the identical mice. By the repeated topical applications of benzo[a]pyrene, the incidence of skin cancer was higher in the DBA/2 mice than in the C3H/He mice. The relationship between the induction of aryl hydrocarbon hydroxylase and carcinogenicity in the skin is briefly discussed.