MorphGlaze: Point of Detection Device for the estimation of Morpholine on coated fruits and vegetables

Besides the fact that it rhymes, it was never stated which apple do we like to eat, does it a bright red wax coated or ungloss fresh/natural one? Morpholine is a common solvent and emulsifier to give an “attractive look” to fruits/vegetables to help them last longer and remains shiny and fresh even during prolonged transit. Morpholine alone does pose a health risk but when it combines with atmospheric and dietary nitrates, it forms the potent carcinogen N-nitrosomorpholine (NMOR). Excessive formation of NMOR can cause multiple primary neoplasms in the respiratory, upper digestive tracts, and liver.

Pathophysiological effects of cadmium(II) on human health-a critical review

Cadmium(II) is an omnipresent environmental toxicant emitted from various industrial sources and by anthropogenic sources such as smoking. Cadmium(II) enters our body through various sources including contaminated food and drinks and from active or passive smoking. It spares no organs in our body and the calamities it invites include primarily nephrotoxicity, osteotoxicity, teratogenicity, endocrine disruption, hepatotoxicity and carcinogenicity above all. It brings about a bolt from the blue in the cellular biochemistry by generating reactive oxygen species (ROS), disrupting the factors involved in the repair of DNA lesions and many other toxic nuisances otherwise by modulating the cell signalling machinery and acting as a potent carcinogen above all. In this review, we have tried to decipher some of the mechanisms played by cadmium(II) in exhibiting its toxic effects on various system of our body.

Unsafe at Low Levels: Adopt a Federal MCL for 1,2,3-Trichloropropane in United States’ Drinking Water

1,2,3-trichloropropane (TCP) is a toxic, man-made chemical used widely in agricultural and other contexts from the 1940s to the 1980s. TCP has settled into the groundwater supplies nearly everywhere it was used. In 2009, the Environmental Protection Agency (EPA) included TCP on the Third Contaminant Candidate list (CCL3) and listed the safe oral reference dose (RfD) for TCP at 0.004 milligrams per kilogram per day. Since then, we have learned that the scope of the TCP contamination problem is greater than first understood. At least 13 states and one territory have contaminated wells. Animal studies show that TCP is a potent carcinogen, and toxicology studies suggest that TCP is unsafe at levels at and above its 5 ppt detection limit. Three states, California, Hawaii, and New Jersey have adopted enforceable maximum contaminant levels of TCP in groundwater. As other states become aware of contamination levels, it is likely that some of them will also regulate TCP, but that could take many years. Federal legislation could mandate EPA advisories sooner than state legislation. The EPA has used the detection limit as the maximum for at least one other chemical, 1,2-Dibromo-3-chloropropane (DBCP), a common co-contaminant of TCP. We recommend that the EPA adopt TCP’s lowest detection level, 5 ppt, as the federal maximum contaminant level

Detection of aflatoxin B1 adducts in Mexican women with cervical lesions

Cervical cancer (CC) is one of the most serious threats to the lives of women; co-factors in addition to oncogenic human papillomavirus (HPV) infection may be important in causing CC. Women in Mexico are exposed to dietary aflatoxin B1, a potent carcinogen, which may act as a co-factor, in inducing progression to CC. Scarce studies are addressing environmental risks associated with the development of CC, thus the study aimed to establish a relationship between the presence of AFB1 and the detection of human papillomavirus in the genome of Mexican women. Forty samples from cervical tissue of women infected with HPV were obtained; positive results regarding the HPV type (16 and/or 18) were found in 92.5% women and the presence of AFB1-DNA adducts were detected in 77.5% of the same positive HPV samples. Detection of AFB1-DNA adducts and genomic concentrations were correlated with the detection of two oncogenic types of HPV 16 and 18. AFB1-DNA positivity and higher genomic concentrations of AFB1-DNA adducts were correlated with an increased risk of oncogenic detection of HPV in cervical samples from women in Mexico. As a secondary objective, a hypothetical interaction of the adducts with the NRF2 pathway has been proposed, therefore activation of p62 and in turn E6 and E7 (HPV proteins) would inhibit the formation of autophagosomes, which would result in a presence or recurrence of CC.

CYP1A2, 2A13, and 3A4 network and interaction with aflatoxin B1

Aspergillus fungi are known to produce aflatoxins, among which aflatoxin B1 (AFB1) is the most potent carcinogen that is metabolised by cytochrome P450 (CYP450). In the liver, AFB1 is metabolised into exo-8,9-epoxide by the CYP1A2 enzymes. The resulting epoxide can react with guanine to cause DNA damage. Natural inhibitors are being identified. However, the modes of action are poorly understood. In the current study, we have investigated the mode of action of AFB1 with CYP1A2, CYP3A4 and CYP2A13 using molecular dynamic simulation (MD simulation) approaches. The interaction network and paths among CYP1A2, CYP3A4, and CYP2A13 have been investigated using the STRING database and PathLinker plugin of Cytoscape. CYP3A4 is the most active protein involved in interactions with AFB1 during its metabolism. Residues 362ARG, 445SER, 450LEU and 451PHE of CYP1A2 are important, interacting with AFB1 and converting it to toxic exo-AFB1-8,9-epoxide (AFBEX). The pathway shows that microsomal epoxide hydrolase (EPHX1) may acts as initiator in the signalling pathway where CYP1A2, CYP3A4 and CYP2A13 interact in a sequential order. The interaction network shows there to be a strong association in expression among CYP1A2, CYP3A4 and CYP2A13 along with other metabolising enzymes. The complex of AFB1 and CYP1A2 was found to be stable during the MD simulation. This study provides a better understanding of the mode of action between AFB1 and CYP1A2, CYP3A4 and CYP2A13 which relates to the effective management of AFB1 toxicity. EPHX1 in the protein network may be an ideal target when designing inhibitors to prevent the toxin’s activation. Peptide inhibitors may be designed to block the substrate site residues of CYP1A2 in order to prevent the conversion from AFB1 into AFBEX. This would either neutralise or reduce its toxicity.

The Frequency of Sex: Population Genomics Reveals Differences in Recombination and Population Structure of the Aflatoxin-Producing Fungus Aspergillus flavus

ABSTRACT The apparent rarity of sex in many fungal species has raised questions about how much sex is needed to purge deleterious mutations and how differences in frequency of sex impact fungal evolution. We sought to determine how differences in the extent of recombination between populations of Aspergillus flavus impact the evolution of genes associated with the synthesis of aflatoxin, a notoriously potent carcinogen. We sequenced the genomes of, and quantified aflatoxin production in, 94 isolates of A. flavus sampled from seven states in eastern and central latitudinal transects of the United States. The overall population is subdivided into three genetically differentiated populations (A, B, and C) that differ greatly in their extent of recombination, diversity, and aflatoxin-producing ability. Estimates of the number of recombination events and linkage disequilibrium decay suggest relatively frequent sex only in population A. Population B is sympatric with population A but produces significantly less aflatoxin and is the only population where the inability of nonaflatoxigenic isolates to produce aflatoxin was explained by multiple gene deletions. Population expansion evident in population B suggests a recent introduction or range expansion. Population C is largely nonaflatoxigenic and restricted mainly to northern sampling locations through restricted migration and/or selection. Despite differences in the number and type of mutations in the aflatoxin gene cluster, codon optimization and site frequency differences in synonymous and nonsynonymous mutations suggest that low levels of recombination in some A. flavus populations are sufficient to purge deleterious mutations. IMPORTANCE Differences in the relative frequencies of sexual and asexual reproduction have profound implications for the accumulation of deleterious mutations (Muller’s ratchet), but little is known about how these differences impact the evolution of ecologically important phenotypes. Aspergillus flavus is the main producer of aflatoxin, a notoriously potent carcinogen that often contaminates food. We investigated if differences in the levels of production of aflatoxin by A. flavus could be explained by the accumulation of deleterious mutations due to a lack of recombination. Despite differences in the extent of recombination, variation in aflatoxin production is better explained by the demography and history of specific populations and may suggest important differences in the ecological roles of aflatoxin among populations. Furthermore, the association of aflatoxin production and populations provides a means of predicting the risk of aflatoxin contamination by determining the frequencies of isolates from low- and high-production populations.

Organ toxicity of diethylnitrosamine and capsaicin in mice – in vivo study

Diethylnitrosamine (DEN) is proven to be toxic to kidneys and liver and to act as a potent carcinogen mainly in liver. Capsaicin (CAP) is an alkaloid produced by Capsicum genus plants and is considered to be a protective agent against toxicity and carcinogenicity of many substances including DEN. The aim of this study was to assess the toxicity of DEN and CAP in liver and kidneys in mice. The experiment started after two weeks of acclimatisation and was conducted according to the Czech animal welfare protection legal guidelines. At the end of the experiment the mice were sacrificed and the toxicity of DEN and CAP in liver and kidneys were analysed. The histopathological examination of the liver revealed multifocal lymphoplasmacytic reaction in parenchyma in DEN treated group. CAP used as both preventive and therapeutic agent caused reduction in number and extent of lesions. In CAP group mitotic figures were found indicating xenobiotic-induced hepatotoxicity or regenerative changes. In the kidneys DEN revealed also multifocal lymphoplasmacytic reaction that has been mitigated by CAP. Moreover histopathological observation of the kidney in DEN group has revealed granular dystrophy of the renal tubules which has not been presented in CAP treated mice. Levels of ALT, AST activity, total protein and albumin concentration was not statistically different among control and experimental groups. In this study mild protective effect of CAP on DEN-induced hepatotoxicity and nephrotoxicity was shown only in histopathological changes. The toxicity of CAP itself is questionable and further studies should be performed to verify its chemopreventive potential.

Quinoline. Documentation of proposed values of occupational exposure limits (OELs)

Quinoline is a colorless hygroscopic liquid with a pungent odor. It darkens with age. It is soluble in alcohol, ether, benzene and carbon disulfide, and is slightly soluble in water. It is used as a solvent and a decarboxylation reagent, and as a raw material in manufacturing dyes, antiseptics, fungicides, niacins and pharmaceuticals. The occupational exposure to quinoline applies to a person involved in the production of the substance or using products manufactured from this substance. The primary routes of potential human exposure to quinoline are ingestion, inhalation, and dermal contact. The most common symptoms of poisoning include eye and skin irritation, damage to the cornea, the retina or optic nerve, headaches and dizziness. Quinoline produced mutations in bacteria in the presence of metabolic activation, unscheduled DNA synthesis in rat hepatocytes, and DNA adducts. Studies of carcinogenicity in animals indicated that administration of quinoline (in feed) increased significantly the incidence of vascular tumors (hemangiomas or hemangiosarcomas) of the liver. Quinoline is classifield as mutagenic category 2 (substance, which is consider as mutagenic to humans) and to category 1B of carcinogenic substances (potent carcinogen to humans – may cause cancer). According to the above data, the MAC value for quinoline was established at 0.6 mg/m3. MAC- -STEL value was not established. The substance was labeled with “sk” (absorption through the skin can be similarly important as inhalation) and “I” – irritant substance.