Understanding exposomes and its relation with cancer risk in Malaysia based on epidemiological evidence: a narrative review.

The prevalence of cancer is increasing globally, and Malaysia is no exception. The exposome represents a paradigm shift in cancer research, emphasizing the importance of a holistic approach that considers the cumulative effect of diverse exposures encountered throughout life. The exposures include dietary factors, air and water pollutants, occupational hazards, lifestyle choices, infectious agents and social determinants of health. The exposome concept acknowledges that each individual's cancer risk is shaped by not only their genetic makeup but also their unique life experiences and environmental interactions. This comprehensive review was conducted by systematically searching scientific databases such as PubMed, Scopus and Google Scholar, by using the keywords "exposomes (environmental exposures AND/OR physical exposures AND/OR chemical exposures) AND cancer risk AND Malaysia", for relevant articles published between 2010 and 2023. Articles addressing the relationship between exposomes and cancer risk in the Malaysian population were critically evaluated and summarized. This review aims to provide an update on the epidemiological evidence linking exposomes with cancer risk in Malaysia. This review will provide an update for current findings and research in Malaysia related to identified exposomes-omics interaction and gap in research area related to the subject matter. Understanding the interplay between complex exposomes and carcinogenesis holds the potential to unveil novel preventive strategies that may be beneficial for public health.

Some relevant mitigating agents of chronic aflatoxin exposure: a treatise.

Aflatoxins, a group of toxic secondary metabolites produced by Aspergillus species, pose significant threats to human health due to their potent carcinogenic, mutagenic, and immunosuppressive properties. Chronic exposure to these contaminants, commonly found in staple foods such as maize and groundnuts, has been linked to an increased risk of liver cancer, growth impairment, and immune dysfunction. Several agents, such as calcium montmorillonite clay and Lactobacillus rhamnosus GG, have shown promise in reducing aflatoxin bioavailability and alleviating its toxic effects. Additionally, dietary supplements such as chlorophyllin, selenium, and N-acetylcysteine have demonstrated potential as adjuvants to counteract aflatoxin-induced oxidative stress and support liver function. In this treatise, some of the most discussed approaches to mitigating aflatoxin effects are explored in terms of their efficacy, safety, and potential mechanisms of action, which include direct aflatoxin binding, detoxification, cellular antioxidative, and hepatocellular protection properties. However, the effectiveness of these strategies can be influenced by various factors, such as dose, duration of exposure, and individual susceptibility. Therefore, further research is needed to optimize these interventions and develop new, targeted therapies for the prevention and treatment of aflatoxin-related diseases. This review aims to provide a comprehensive analysis of 18 pharmaceutical, nutraceutical, supplement, and probiotic strategies currently available for mitigating the deleterious effects of chronic aflatoxin exposure in humans and animal models.

Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts.

Utilizing the atto-zeptomole sensitivity of UPLC-accelerator mass spectrometry (UPLC-AMS), we previously demonstrated significant first-pass metabolism following escalating (25-250 ng) oral micro-dosing in humans of [14C]-benzo[a]pyrene ([14C]-BaP). The present study examines the potential for supplementation with Brussels sprouts (BS) or 3,3'-diindolylmethane (DIM) to alter plasma levels of [14C]-BaP and metabolites over a 48-h period following micro-dosing with 50 ng (5.4 nCi) [14C]-BaP. Volunteers were dosed with [14C]-BaP following fourteen days on a cruciferous vegetable restricted diet, or the same diet supplemented for seven days with 50 g of BS or 300 mg of BR-DIM® prior to dosing. BS or DIM reduced total [14C] recovered from plasma by 56-67% relative to non-intervention. Dietary supplementation with DIM markedly increased Tmax and reduced Cmax for [14C]-BaP indicative of slower absorption. Both dietary treatments significantly reduced Cmax values of four downstream BaP metabolites, consistent with delaying BaP absorption. Dietary treatments also appeared to reduce the T1/2 and the plasma AUC(0,∞) for Unknown Metabolite C, indicating some effect in accelerating clearance of this metabolite. Toxicokinetic constants for other metabolites followed the pattern for [14C]-BaP (metabolite profiles remained relatively consistent) and non-compartmental analysis did not indicate other significant alterations. Significant amounts of metabolites in plasma were at the bay region of [14C]-BaP irrespective of treatment. Although the number of subjects and large interindividual variation are limitations of this study, it represents the first human trial showing dietary intervention altering toxicokinetics of a defined dose of a known human carcinogen.

Integrated approach towards acrylamide reduction in potato-based snacks: A critical review.

Acrylamide is a process contaminant and neurotoxic with growing evidence of cancer in human. Potato-based products majorly contribute towards acrylamide dietary intake thereby posing major food safety threat that necessitates formulation of acrylamide reduction strategies. This review highlights the recent research work on acrylamide formation mechanism, dietary intake, toxicity and potential reduction strategies at various levels in the food supply chain to ensure safety of potato-based products. Acrylamide formation in potato-based products depends on several factors involved in potato supply chain. Depending on the variety, application of nitrogen and sulphur fertilization may show positive, negative, or no effect on acrylamide formation. Heat and water stress faced by potato crops may increase the risk of acrylamide formation in processed products. Various pre-processing (e.g., blanching, chemical treatments etc.) and processing (e.g., methods, temperature, time) strategies may also reduce acrylamide formation (37-98%) in potato-based products at commercial and domestic levels. The acrylamide reduction strategies from farm to fork level have been discussed with special emphasis on mechanism of chemical treatments with pictorial representation.

The Chemopreventive Effects of Polyphenols and Coffee, Based upon a DMBA Mouse Model with microRNA and mTOR Gene Expression Biomarkers.

Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea (Camellia sinensis) extract, polyphenol extract (a mixture of blackberry (Rubus fruticosus), blackcurrants (Ribes nigrum), and added resveratrol phytoalexin), Chinese bayberry (Myrica rubra) extract, and a coffee (Coffea arabica) extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and mTOR gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely RAS and MYC. The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced PTEN as well as SIRT tumor suppressor genes.

Safest Roasting Times of Coffee To Reduce Carcinogenicity.

ABSTRACT: Roasting coffee results in not only the creation of carcinogens such as acrylamide, furan, and polycyclic aromatic hydrocarbons but also the elimination of carcinogens in raw coffee beans, such as endotoxins, preservatives, or pesticides, by burning off. However, it has not been determined whether the concentrations of these carcinogens are sufficient to make either light or dark roast coffee more carcinogenic in a living organism. An Ames test was conducted on light, medium, and dark roast coffee from three origins. We found that lighter roast coffee shows higher mutagenicity, which is reduced to the control level in dark roast coffee varieties, indicating that the roasting process is not increasing mutagenic potential but is beneficial to eliminating the existing carcinogens in raw coffee beans. This result suggests that dark roast coffee is safer and promotes further studies of the various carcinogens in raw coffee that have been burned off.

Health Risk Assessment of Exposure to Trace Elements from Drinking Black and Green Tea Marketed in Three Countries.

Although tea can be beneficial for our health, consuming excess trace elements in tea can be harmful. In this study, the carcinogenic and noncarcinogenic health risk for trace elements in tea influenced by the country of origin, tea type, and infusion process was assessed. Tea (Camellia sinensis) purchased from China, India, and the USA, including black and green tea, were analyzed for essential micronutrients (Cu, Se, and Zn) and nonessential trace elements (Ag, As, Ba, Cd, Cr, and Pb) in leaves and three types of infusions. The results showed that country of origin, tea type, and infusion process had a significant influence on the trace element contents in tea leaves and infusions, also on health risk. Country of origin had a significant influence on Ba, Cr, Pb, and Zn contents in tea leaves and on As, Ba, Cd, Cr, Pb, and Zn contents in tea infusions. Black tea had significantly higher (p < 0.05) Cr and Cu content in tea leaves than green tea, but only Cr content was significantly higher (p < 0.05) than that of green tea in tea infusion. The trace element contents were the highest in the first infusion and decreased as the number of infusion steps increased. The results showed that the consumption of tea infusion was not likely to cause noncarcinogenic risk. However, the carcinogenic risk for As was of concern. Our results indicate that avoiding drinking the first infusion can help to reduce both carcinogenic and noncarcinogenic health risks for trace elements.

Meta-Analysis of the Association between Asbestos Exposure and Esophageal Cancer.

BACKGROUND: We conducted a meta-analysis to quantitatively assess the association between asbestos exposure and esophageal cancer. METHODS: We systematically collected articles from three electronic databases and calculated the pooled standardized mortality rate (SMR) from the meta-analysis. Subgroup analysis according to the type of asbestos exposure, follow-up years, sample size, industry classification, sex, and high-dose exposure was conducted. RESULTS: From 242 studies, 34 cohort studies were included in our meta-analysis. Pooled SMR was positively associated with asbestos exposure and esophageal cancer (pooled SMR = 1.28; 95% confidence interval (CI) 1.19-1.38, p < 0.00001). In the subgroup analysis, (1) chrysolite, (2) four groups with follow-up over ten years, (3) the textile industry and shipyard, (4) both male and female, and (5) eight studies on highest asbestos exposure, all the subgroups showed significantly increased pooled SMRs. CONCLUSION: Asbestos exposure was significantly and positively associated with esophageal cancer, especially chrysolite. Considering the long latency period, we suggest that patients should be followed up for cancer, including esophageal cancer, for over ten years.

Chemopreventive role of arabinogalactan against experimentally induced pulmonary carcinogenesis: a study in relation to its initiation phase.

The aim of the present study is to divulge the chemopreventive potential of arabinogalactan (AG) on benzo(a)pyrene [B(a)P] induced initiation of lung carcinogenesis. AG is one of the naturally occurring bioactive polysaccharides which is widely found in medicinal plants. Male Balb/c mice were divided into four experimental groups. Group I served as control. Group II animals were injected with B(a)P (50 mg/kg b. wt. i.p.). Group III animals were administered with AG (7.5 mg/kg b.wt.) orally. Group IV animals received B(a)P and AG as in group II and group III, respectively. B(a)P treatment in mice resulted in imbalance of carcinogen metabolizing enzymes and respiratory marker enzymes at 2nd, 6th and 10th week of the experimental protocol. Also, it leads to the increased protein synthesis as depicted by increased argyrophilic nucleolar organizer regions (AgNOR) positive cells and altered histopathological features. Studies on bronchoalveolar lavage fluid (balf) of B(a)P exposed animals revealed increase in surface tension when compared with control counterparts. Apart from target tissue (lung), B(a)P also led to the clastogenic damage in other tissues (spleen and bone marrow) as depicted by increase in percentage of micronucleus cells at different time intervals. Treatment with AG efficiently counteracted all the above anomalies and restored cellular homeostasis. These observations suggest that AG has the potential to modulate B(a)P induced changes in the pulmonary tissue as well as other tissues which could have implications in delaying the initiation of carcinogenesis, however, further investigations are required to explore its complete mechanism of action.

Single source precursor synthesized CuS nanoparticles for NIR phototherapy of cancer and photodegradation of organic carcinogen.

Herein, we report cost effective and body compatible CuS nanoparticles (NPs) derived from a single source precursor as photothermal agent for healing deep cancer and photocatalytic remediation of organic carcinogens. These NPs efficiently kill MCF7 cells (both in vivo and in vitro) under NIR irradiation by raising the temperature of tumor cells. Such materials can be used for the treatment of deep cancer as they can produce a heating effect using high wavelength and deeply penetrating NIR radiation. Furthermore, CuS NPs under solar light irradiation efficiently convert p-nitrophenol (PNP), an environmental carcinogen, to p-aminophenol (PAP) of pharmaceutical implication. In a nutshell, CuS can be used for the treatment of deep cancer and for the remediation of carcinogenic pollutants. There seems an intrinsic connection between the two functions of CuS NPs that need to be explored in length.

Fifty Years of Research and One Conclusion: Opium Causes Cancer.

In September 2020, the International Agency for Research on Cancer (IARC) announced that opium consumption causes cancer in humans - a conclusion drawn after reviewing data from five decades of research. Given the widespread use of opium and its derivatives by millions of people across the world, the classification of opium consumption as a "Group 1" carcinogen has important public health ramifications. In this mini-review, we offer a short history of opium use in humans and briefly review the body of research that led to the classification of opium consumption as carcinogenic. We also discuss possible mechanisms of opium's carcinogenicity and potential avenues for future research.

Bacteria as a double-action sword in cancer.

Bacteria have long been known as one of the primary causative agents of cancer, however, recent studies suggest that they can be used as a promising agent in cancer therapy. Because of the limitations that conventional treatment faces due to the specific pathophysiology and the tumor environment, there is a great need for the new anticancer therapeutic agents. Bacteriotherapy utilizes live, attenuated strains or toxins, peptides, bacteriocins of the bacteria in the treatment of cancer. Moreover, they are widely used as a vector for delivering genes, peptides, or drugs to the tumor target. Interestingly, it was found that their combination with the conventional therapeutic approaches may enhance the treatment outcome. In the genome editing era, it is feasible to develop a novel generation of therapeutic bacteria with fewer side effects and more efficacy for cancer therapy. Here we review the current knowledge on the dual role of bacteria in the development of cancer as well as cancer therapy.

Biotransformation and Toxicities of Aristolochic Acids.

Environmental and iatrogenic exposures contribute significantly to human diseases, including cancer. The list of known human carcinogens has recently been extended by the addition of aristolochic acids (AAs). AAs occur primarily in Aristolochia herbs, which are used extensively in folk medicines, including Traditional Chinese Medicine. Ingestion of AAs results in chronic renal disease and cancer. Despite importation bans imposed by certain countries, herbal remedies containing AAs are readily available for purchase through the internet. With recent advancements in mass spectrometry, next generation sequencing, and the development of integrated organs-on-chips, our knowledge of cancers associated with AA exposure, and of the mechanisms involved in AA toxicities, has significantly improved. DNA adduction plays a central role in AA-induced cancers; however, significant gaps remain in our knowledge as to how cellular enzymes promote activation of AAs and how the reactive species selectively bind to DNA and kidney proteins. In this review, I describe pathways for AAs biotransformation, adduction, and mutagenesis, emphasizing novel methods and ideas contributing to our present understanding of AA toxicities in humans.

Interactions between phytochemicals from fruits and vegetables: Effects on bioactivities and bioavailability.

The combinations of two or more phytochemicals bring about changes in the ultimate biological effects and/or the bioavailability of each component. A number of mixtures of pure bioactive compounds or phytochemical-containing plant extracts provide synergy with regard to antioxidant status, anti-inflammation, anti-cancer and chemoprevention of several oxidative stress and metabolic disorders in vitro. The biological activities of food phytochemicals depend upon their bioaccessibility and bioavailability which can be affected by the presence of other food components including other bioactive constituents. The interactions between phytochemicals during intestinal absorption could result in changes in the bioavailability of the compounds, which in turn affects the intensity of their bioactivities. This paper provides an overview of combined biological effects of phytochemical mixtures derived from fruits and vegetables with a focus on anti-oxidative, anti-inflammatory and anti-carcinogenic activities. The bioavailability impairment or enhancement caused by the co-consumption of dietary phytochemicals is also discussed. Finally, research gaps for future studies on phytochemical interactions are identified.

[Vitamin D and UV protection]. / Vitamin D und UV-Schutz.

A high percentage of people present with reduced vitamin D3 levels. Reduced vitamin D3 levels have to be supplemented. Oral supplementation can be performed easily and without significant side effects. Because vitamin D3 can be produced in the skin via ultraviolet B (UVB) irradiation, it is possible to elevate reduced vitamin D3 levels by UVB exposure. However, UVB, which is classified as a complete carcinogen, induces skin cancer. Therefore, UVB irradiation should not be utilized to stimulate vitamin D3 synthesis. Sun protection, especially wearing of clothes and seeking shade and appropriate use of sunscreens, correlates with reduced D3 levels. A risk-benefit calculation shows that oral supplementation of vitamin D3 is preferred to UVB/sun expsure to increase serum vitamin D3 levels.

Thirdhand smoke beliefs and behaviors among healthcare professionals.

Thirdhand smoke (THS) refers to tobacco smoke contaminants and by-products that remain in the environment after a cigarette is extinguished. The purpose of this study was to assess beliefs and behaviors regarding THS among healthcare professionals, and to examine associations among smoking attitudes/beliefs, provider demographics, and THS beliefs and behaviors. Healthcare professionals (N = 204) at a comprehensive cancer center and affiliated general hospital in a northeastern urban area completed online questionnaires. About one third of the respondents had heard of THS before completing the survey, and more than two thirds of the sample believed that THS issues do not receive enough attention. Being female, likelihood of discussing THS with others, endorsing the belief that smoking affects the quality of parenting, and support for government action towards smoking bans were significantly associated with providers' belief that THS is harmful. Endorsing the belief that smoking affects the quality of parenting and belief that THS is harmful were significantly associated with the likelihood of discussing THS with others. Findings shed light on THS beliefs and behaviors of healthcare providers (a group of individuals that could be trained to educate and advise patients about THS) and inform recommendations for new tobacco policies and clinical guidelines for best practices in tobacco control and prevention.

Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation.

Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8-10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF-κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK-induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF-κB and CYP2E1 in the liver and attenuated the NNK-induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen-associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen-induced pulmonary and hepatic injury.

MODULATION OF CARCINOGEN-METABOLIZING ENZYME BY MADINAH MINT (Mentha spp) IN RAT LIVER.

BACKGROUND: The present study was undertaken to assess whether boiling water mint extract (BWME) modulates the cytochrome P450 mixed function oxidase system. MATERIALS AND METHODS: Male albino rats were randomly divided into two groups, comprising 12 animals each. The first group served as control, whereas the second was maintained on BWME (10 % w/v) as its sole drinking liquid for six weeks. Liver microsomal were separated and subjected for phase I and II enzymes (cytochrome P450 mixed function oxidase) analysis. RESULTS: The results obtained showed that, BWME caused a significant elevation in the activity of epoxide hydrolase (p<0.001) when compared with the control. However, glutathione S-transferase and glucuronosyl transferase activities were significantly decreased (p<0.001 and p<0.01) respectively compared with control. The mutagenic activity of N-nitrosopiperidine was lower in the mint-treated hepatic microsomal compared with the controls. CONCLUSION: It can be concluded that BWME has the potential to suppress the activity of cytochrome enzymes involved in the bio-activation of chemical carcinogen; hence may display chemo preventive activity.

Aristolochic acids - Induced transcriptomic responses in rat renal proximal tubule cells in vitro.

Aristolochic acids (AAs) are the active components of herbal drugs derived from Aristolochia species that have been used for medicinal purposes since antiquity. However, AAs have recently been discovered to be highly nephrotoxic and induced urothelial cancer in humans and malignant tumors in the kidney and urinary tract of rodents. In this study, we exposed rat renal proximal tubule cells in vitro to a sub-cytotoxic level of AAs at three different time points (6 h, 24 h and 72 h). We then analyzed the gene expression profile after the compound exposure. Functional analysis with Ingenuity Pathways Analysis and DAVID tools revealed that at the late time point (72 h) there are many significantly altered genes involved in cancer-related pathways such as p53 signaling. MIAMI-compliant microarray data are deposited in the NCBI GEO database under accession number GSE68687 and can be found at: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68687.

Animal models of disease: pre-clinical animal models of cancer and their applications and utility in drug discovery.

Preclinical models of human cancers are indispensable in the drug discovery and development process for new cancer drugs, small molecules and biologics. They are however imperfect facsimiles of human cancers given the genetic and epigenetic heterogeneity of the latter and the multiplicity of dysregulated survival and growth-regulatory pathways that characterize this spectrum of diseases. This review discusses pre-clinical tumor models - traditional ectopic xenografts, orthotopic xenografts, genetically engineered tumor models, primary human tumorgrafts, and various multi-stage carcinogen-induced tumor models - their advantages, limitations, physiological and pathological relevance. Collectively, these animal models represent a portfolio of test systems that should be utilized at specific stages in the drug discovery process in a pragmatic and hierarchical manner of increasing complexity, physiological relevance, and clinical predictability of the human response. Additionally, evaluating the efficacy of novel therapeutic agents emerging from drug discovery programs in a variety of pre-clinical models can better mimic the heterogeneity of human cancers and also aid in establishing dose levels, dose regimens and drug combinations for use in clinical trials. Nonetheless, despite the sophistication and physiological relevance of these human cancer models (e.g., genetically engineered tumor models and primary human tumografts), the ultimate proof of concept for efficacy and safety of novel oncology therapeutics lies in humans. The judicious interpretation and extrapolation of data derived from these models to humans, and a correspondingly greater emphasis placed on translational medical research in early stage clinical trials, are essential to improve on the current clinical attrition rates for novel oncology therapeutic agents.