Relevance of Carcinogen-Induced Preclinical Cancer Models.

Chemical agents can cause cancer in animals by damaging their DNA, mutating their genes, and modifying their epigenetic signatures. Carcinogen-induced preclinical cancer models are useful for understanding carcinogen-induced human cancers, as they can reproduce the diversity and complexity of tumor types, as well as the interactions with the host environment. However, these models also have some drawbacks that limit their applicability and validity. For instance, some chemicals may be more effective or toxic in animals than in humans, and the tumors may differ in their genetics and phenotypes. Some chemicals may also affect normal cells and tissues, such as by causing oxidative stress, inflammation, and cell death, which may alter the tumor behavior and response to therapy. Furthermore, some chemicals may have variable effects depending on the exposure conditions, such as dose, route, and duration, as well as the animal characteristics, such as genetics and hormones. Therefore, these models should be carefully chosen, validated, and standardized, and the results should be cautiously interpreted and compared with other models. This review covers the main features of chemically induced cancer models, such as genetic and epigenetic changes, tumor environment, angiogenesis, invasion and metastasis, and immune response. We also address the pros and cons of these models and the current and future challenges for their improvement. This review offers a comprehensive overview of the state of the art of carcinogen-induced cancer models and provides new perspectives for cancer research.

Reduction of Management Costs and Avoidance of Air Release of Carcinogens Through a Waste Segregation Program in a Brazilian Medical Institution.

Hospital waste management is a current sustainability challenge. Although not always performed, the most applied approach in current protocols is the proper segregation of waste. The incineration of hospital waste is an significant source of emission of specific toxic particles and gases. We highlighted dioxins, whose representatives have been considered carcinogenic agents since 1994. Several experimental and epidemiologic studies have shown greater cancer morbidity and mortality associated with dioxin exposure. In the present study, we presented the impact of a hospital waste management program implemented in an oncology institution based on proper segregation and consequent reduction of incinerated mass. Data were collected for 8 years and the waste was separated into five categories: infectious (A4), chemical (B), recyclable (DR), non-recyclable (DNR), and sharps (E). The classes addressed to incineration were A4, B, and E. A team education starting from the admission process and with a continued education program was essential for a successfully implemented program. We achieved a 66% saving of waste from incineration, equivalent to 76 tons, of which 71.9 tons corresponded to recyclable waste. If the waste separation protocol was not implemented, the biohazardous and chemical material would contaminate the rest of the residues, making incineration as a final destination mandatory for all the waste. This scenario would result in significantly more dioxins release and a 64% higher cost of waste management. This low-cost implementation measure was effective in the cost reduction of waste management and minimization of air release of human carcinogens.

Cytostatics as hazardous chemicals in healthcare workers' environment.

Cytostatics not only induce significant side-effects in patients treated oncologically but also pose a threat to the health of occupationally exposed healthcare workers: pharmacists, physicians, nurses and other personnel. Since the 1970s numerous reports from various countries have documented the contamination of working areas with cytostatics and the presence of drugs/metabolites in the urine or blood of healthcare employees, which directly indicates the occurrence of occupational exposure to these drugs. In Poland the significant scale of occupational exposure to cytostatics is also confirmed by the data collected in the central register of occupational carcinogens/mutagens kept by the Nofer Institute of Occupational Medicine. The assessment of occupational exposure to cytostatics and health risks constitutes employers' obligation. Unfortunately, the assessment of occupational risk resulting from exposure to cytostatics raises a number of concerns. Provisions governing the problem of workers' health protection are not unequivocal because they derive from a variety of law areas, especially in a matter of hazard classification and safety data sheets for cytostatics. Moreover, no legally binding occupational exposure limits have been set for cytostatics or their active compounds, and analytical methods for these substances airborne and biological concentrations are lacking. Consequently, the correct assessment of occupational exposure to cytostatics, the evaluation of health hazards and the development of the proper preventive strategy appear difficult. The authors of this article described and discussed the amendments to the European provisions concerning chemicals in the light of employers' obligations in the field of employees' heath protection against the consequences of exposure to cytostatics. Some modifications aimed at a more effective health protection of workers occupationally exposed to cytostatics were also proposed. Int J Occup Med Environ Health. 2019;32(2):141-59.

Gender differences in occupational exposure to carcinogens among Italian workers.

BACKGROUND: Many carcinogenic chemicals are still used or produced in several economic sectors. The aim of this study is to investigate differences in occupational exposure patterns to carcinogens by gender in Italy. METHODS: Information about the most common carcinogens recorded in the Italian occupational exposures database (SIREP) for the period 1996-2015 was retrieved. Descriptive statistics were calculated for exposure-related variables (carcinogenic agent, occupational group, economic activity sector, and workforce size). The chi-square(χ2) test was used to verify differences between genders, and logistic regression analysis was performed to evaluate the association between gender and risk of having higher exposure levels, after adjusting for age. Concurrent exposures to multiple carcinogens were investigated using the two-step cluster analysis. RESULTS: A total of 166,617 exposure measurements were selected for 40 different carcinogens. Exposed workers were only in a small proportion women (9%), and mostly aged 20-44 years (70%) in both genders. Women were more likely to be exposed than men to higher levels for several carcinogens even after correction for age at exposure, and the exposure level was significantly (p < 0.01) associated with occupation, economic sector and workforce size. The five main clusters of co-exposures identified in the entire dataset showed a differential distribution across economic sectors between genders. CONCLUSIONS: The exposures to occupational carcinogens have distinguishing characteristics in women, that are explained in part by work and job segregation. Because of the presence of high-exposed groups of female workers in many industrial sectors, further research and prevention efforts are recommended.

Relevance of iodine intake as a reputed predisposing factor for thyroid cancer

Iodine is a trace element that is essential for the synthesis of thyroid hormone. Both chronic iodine deficiency and iodine excess have been associated with hypertrophy and hyperplasia of follicular cells, attributed to excessive secretion of TSH. This may be associated to thyroid cancer risk, particularly in women. Experimental studies have documented thyroid cancer induction by elevation of endogenous TSH, although in a small number of animals. Iodine deficiency associated with carcinogenic agents and chemical mutagens will result in a higher incidence of thyroid malignancy. Inadequate low iodine intake will result in increased TSH stimulation, increased thyroid cell responsiveness to TSH, increased thyroid cell EGF-induced proliferation, decreased TGFbeta 1 production and increased angiogenesis, all phenomena related to promotion of tumor growth. Epidemiological studies associating iodine intake and thyroid cancer led to controversial and conflicting results. There is no doubt that introduction of universal iodine prophylaxis in population previously in chronic iodine-deficiency leads to a changing pattern of more prevalent papillary thyroid cancer and declining of follicular thyroid cancer. Also anaplastic thyroid cancer is practically not seen after years of iodine supplementation. Iodine excess has also been indicated as a possible nutritional factor in the prevalence of differentiated thyroid cancer in Iceland, Hawaii and, more recently, in China. In conclusion: available evidence from animal experiments, epidemiological studies and iodine prophylaxis has demonstrated a shift towards a rise in papillary carcinoma, but no clear relationship between overall thyroid cancer incidence and iodine intake.

O iodo é essencial para a síntese de hormônios tireóideos e tanto a deficiência crônica deste halogeno como o excesso nutricional de iodo levam a hiperplasia e hipertrofia dos elementos foliculares (por excesso de TSH). Esse fenômeno pode se associar a maior risco de câncer de tireóide, especialmente no sexo feminino. Estudos experimentais documentam indução de câncer de tireóide após prolongado excesso circulante de TSH, o qual induz aumento da proliferação celular medida por fator de crescimento epidermal (EGF), decréscimo de síntese de fator de transformação do crescimento (TGFbeta 1) e aumento da angiogenese. Estudos epidemiológicos entre nutrição de iodo e câncer de tireóide são conflitantes. É, todavia, aceito que a correção de prévia deficiência de iodo com aporte nutricional adequado deste halogeno leva à maior prevalência de carcinoma papilífero (e decréscimo de carcinoma folicular). Em alguns países, o excesso de iodo foi apontado como causa aparente de maior prevalência de câncer de tireóide. Em conclusão: não existe uma relação causa-efeito entre iodo nutricional e prevalência de câncer de tireóide, e outros fatores intervenientes ambientais devem ser considerados.

Molecular Mechanisms Underlying Anti-Tumor Promoting Activities of Heat-Processed Panax ginseng C.A. Meyer

Recently, there have been considerable efforts to search for naturally occurring substances that can inhibit, reverse, or retard the multi-stage carcinogenesis. A wide array of phenolic substances derived from edible and medicinal plants have been reported to possess anticarcinogenic and antimutagenic activities and in many cases, the chemopreventive activities of phytochemicals are associated with their anti-inflammatory and/or antioxidative properties. Panax ginseng C.A. Meyer cultivated in Korea has been widely used in traditional herbal medicine for the treatment of various diseases. Certain fractions or purified ingredients of ginseng have been shown to exert anticarcinogenic and antimutagenic activities. Our previous studies have revealed that the methanol extract of heat-processed Panax ginseng C.A. Meyer attenuates the lipid peroxidation in rat brain homogenates and is also capable of scavenging superoxide generated by xanthine- xanthine oxidase or by 12-O-tetradecanoylphorbol-13-acetate (TPA) in differentiated human promyelocytic leukemia (HL-60) cells. Topical application of the same extract onto shaven backs of female ICR mice also suppressed TPA-induced skin tumor promotion. Likewise, topical application of ginsenoside Rg3, one of the constituents of heat-treated ginseng, significantly inhibited TPA-induced mouse epidermal ornithine decarboxylase activity and skin tumor promotion. Expression of cyclooxygenase-2 (COX-2) in TPA-stimulated mouse skin was markedly suppressed by Rg3 pretreatment. In addition, Rg3 inhibited TPA-stimulated activation of NF-kB and extracellular-regulated protein kinase (ERK), one of the mitogen-activated protein (MAP) kinase in mouse skin and also in cultured human breast epithelial cells (MCF-10A).