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Bladder cancer (BCa) and prostate cancer (PCa) are genitourinary cancers which constitute significant health problems in men and in which environmental factors play an important role. Understanding the genetic susceptibility to BCa or PCa and occupational exposure is paramount to improving cancer prevention and early detection. The aim of this review article was to address the scientific evidence on the genetic risk factors and occupational exposure associated with the occurrence of BCa and PCa. The authors identified relevant original articles that have been published between 1994 and 2023. Variations of the following search terms: "gene" and "occupational" combined with one of the following terms: "bladder cancer" or "prostate cancer" were applied for the search purpose. The authors found 342 publications of which 50 population studies met their requirements for gene-occupation interactions. In total, 34 full-text manuscripts were about BCa and 16 about PCa. These research examines the genes involved in detoxification processes of xenobiotics (glutathione S-transferase, N-acetyltransferase, cytochrome P450, UDP-glucuronosyltransferase), oxidative stress (glutathione peroxidase 1, manganese superoxide dismutase, catalase), altering DNA repair capacity (X-ray repair cross-complementing 1, base excision repair, nucleotide excision repair), tumour suppression (TP53 gene), and vitamin D pathway (vitamin D receptor gene). The role of genetic factors in the occupational exposure has not been conclusively established, but it appears the possibility of genetic involvement. Determination of environmentally responsive genes provides important mechanistic implications for the etiology of occupational cancers, and valuable input in occupational exposure limits set by taking genetic susceptibility into account. More genetic research is needed to corroborate these findings and assess their significance in the workplace. Med Pr. 2023;74(2):127-44.

Autorka omawia reportaż Hanny Krall w perspektywie jego obecności w szkolnej dydaktyce języka polskiego (usunięcie z listy lektur, powrót ta nią, obecność w arkuszach maturalnych). Uważa go za książkę ratunkową: to jedna z niewielu lektur aktywujących uczniowską emergencję. Wskazuje także na tropy możliwe do podjęcia podczas zajęć języka polskiego w szkole ponadpodstawowej.

The adoption of Directive 2010/63/EU on the protection of animals used for scientific purposes has given a major push to the formation of Three Rs initiatives in the form of centres and platforms. These centres and platforms are dedicated to the so-called Three Rs, which are the Replacement, Reduction and Refinement of animal use in experiments. ATLA’s 50th Anniversary year has seen the publication of two articles on European Three Rs centres and platforms. The first of these was about the progressive rise in their numbers and about their founding history; this second part focuses on their current status and activities. This article takes a closer look at their financial and organisational structures, describes their Three Rs focus and core activities (dissemination, education, implementation, scientific quality/translatability, ethics), and presents their areas of responsibility and projects in detail. This overview of the work and diverse structures of the Three Rs centres and platforms is not only intended to bring them closer to the reader, but also to provide role models and show examples of how such Three Rs centres and platforms could be made sustainable. The Three Rs centres and platforms are very important focal points and play an immense role as facilitators of Directive 2010/63/EU ‘on the ground’ in their respective countries. They are also invaluable for the wide dissemination of information and for promoting the implementation of the Three Rs in general.

Public awareness and discussion about animal experiments and replacement methods has greatly increased in recent years. The term ‘the Three Rs’, which stands for the Replacement, Reduction and Refinement of animal experiments, is inseparably linked in this context. A common goal within the Three Rs scientific community is to develop predictive non-animal models and to better integrate all available data from in vitro, in silico and omics technologies into regulatory decision-making processes regarding, for example, the toxicity of chemicals, drugs or food ingredients. In addition, it is a general concern to implement (human) non-animal methods in basic research. Toward these efforts, there has been an ever-increasing number of Three Rs centres and platforms established over recent years — not only to develop novel methods, but also to disseminate knowledge and help to implement the Three Rs principles in policies and education. The adoption of Directive 2010/63/EU on the protection of animals used for scientific purposes gave a strong impetus to the creation of Three Rs initiatives, in the form of centres and platforms. As the first of a series of papers, this article gives an overview of the European Three Rs centres and platforms, and their historical development. The subsequent articles, to be published over the course of ATLA’s 50th Anniversary year, will summarise the current focus and tasks as well as the future and the plans of the Three Rs centres and platforms. The Three Rs centres and platforms are very important points of contact and play an immense role in their respective countries as ‘on the ground’ facilitators of Directive 2010/63/EU. They are also invaluable for the widespread dissemination of information and for promoting implementation of the Three Rs in general.

Cadmium (Cd), a heavy metal with strong carcinogenic properties has been linked with breast cancer risk. Epidemiological data on the association between Cd exposure and breast cancer are not consistent and suggest that this relationship may be modulated by a number of different factors. The mechanisms of action underlying the molecular effects of Cd, especially in terms of its carcinogenicity, are generally not well understood. Specifically, in the mammary gland, the effects of Cd are considered to be related mainly to its oestrogenic potential, however, several other mechanisms have also been suggested, such as epigenetic alterations, inhibition of DNA repair pathways, induction of oxidative stress, interference with metallothioneins, cadherins and integrins, as well as interactions with xenobiotics. This review summarizes the current state of knowledge in this field, including potential mechanisms of action of Cd in breast cancer initiation and progression, as well as possible ways of protection against its toxicity. Importantly, there are many research gaps in this area since limited evidence is available from experimental studies. Important issues to be further investigated concern exact molecular mechanisms of Cd accumulation in the tissues and Cd-induced activation of eostrogen receptors. Impact on DNA damage and epigenome upon Cd exposure in breast cancer development remains still highly unexplored area and should gain more interest.

According to the precarious manhood perspective, masculinity threat triggers various compensatory mechanisms and heightens motivation to restore and reaffirm masculinity via typically masculine attitudes and behaviors. Four experiments aiming to examine the effect of masculinity threat on prejudices toward sexual and gender minorities were undertaken, controlling for adherence to sex role stereotypes. Our studies showed that Polish men representing university and high school students exposed to gender threat experienced increased negative affect (Experiment 1) and expressed higher prejudices toward gay people (Experiment 2) and transgender individuals (Experiments 3a and 3b). Furthermore, Experiment 2 revealed an effect of masculinity threat on modern prejudices predominantly toward gay people but not old-fashioned homonegativity. The results are discussed in terms of the role of masculinity threat as the mechanism responsible for gender differences in the attitudes toward sexual and gender minorities.

In the study the modulating effect of inhibition of phosphatidylinositol 3-kinase-related kinases (PIKK): ATM (Ataxia Telangiectasia Mutated), ATR (Ataxia Telangiectasia and Rad3 Related) and DNA-PK (DNA-dependent protein kinase) on genotoxicity of dibenzo[def,p]chrysene (DBC) in HepG2 human hepatocellular cancer cells was investigated. The cytotoxicity of DBC was determined, also in combination with PIKK inhibitors, using the MTT reduction assay. The high cytotoxicity of DBC was observed after 72 h incubation (IC50 = 0.06 μM). The PIKK inhibitors applied at non-cytotoxic concentrations: caffeine (1 mM) and KU55933 (2.5 μM) had no significant influence on the DBC cytotoxicity, however NU7026 (5 μM) caused significant increase in the cell viability by about 25%. The combinations of the inhibitors (double or triple) where NU7026 was present also caused increase in the cell viability (i.e. cytoprotective effect) compared to the effect of DBC. The level of damage to the genetic material (DNA double strand breaks, DSB) was assessed by measuring levels of phosphorylated form of H2A histone (γH2AX) and neutral comet assay. DBC induced DSB in a concentration and time-dependent manner. NU7026 considerably reduced the level of DSB level measured by γH2AX and comet assay. The obtained results confirm that DBC is cytotoxic and causes damage to the genetic material including DSB. The DNA-PK inhibitor NU7026 increases cell viability after exposure to DBC and reduces DNA damage, what indicates an important role of the sensor kinase in mediating the effect.

In this study the role of PI3K/Akt signaling pathway in arsenic trioxide (ATO)-treated parental Jurkat cells and also in derived ATO-resistant clones grown in the presence of given ATO concentration was investigated. ATO-resistant clones (cultured for 8-12weeks in the presence of 1, 2.5 and 5μM ATO) were characterized by high viability in the presence of ATO but slower growth rate compared to the parental cells. Morphological and functional characterization of derived ATO-resistant clones revealed that they did not differ fundamentally from parental Jurkat cells in terms of cell size, level of GSH, the lysosomal fluorescence or CD95/Fas surface antigen expression. However, a slight increase in the mitochondrial potential (JC-1 staining) was detected in the clones compared to parental Jurkat cells. Side population analysis (Vybrant DyeCycle Violet™ staining) in ATO resistant clones did not indicate any enrichment withcancer stem cells. Akt1/2, AktV or wortmannin inhibitors decreased viability of ATO-resistant clones grown in the presence of ATO, with no effect on ATO-treated parental cells. Flow cytometry analysis showed that ATO decreased the level of p-Akt in ATO-treated parental cells, while the resistant clones exhibited higher levels of p-Akt immunostaining than parental Jurkat cells. Expression analysis of 84 genes involved in the PI3K/Akt pathway revealed that this pathway was predominantly active in ATO-resistant clones. c-JUN seems to play a key role in the induction of cell death in ATO-treated parental Jurkat cells, as dose-dependent strong up-regulation of JUN was specific for the ATO-treated parental Jurkat cells. On the other hand, changes in expression of cyclin D1 (CCND1), insulin receptor substrate 1 (IRS1) and protein kinase C isoforms (PRKCZ,PRKCB and PRKCA) may be responsible for the induction of resistance to ATO. The changes in expression of growth factor receptor-bound protein 10 (GRB10) observed in ATO-resistant clones suggest a possibility of induction of different mechanisms in development of resistance to ATO depending on the drug concentration and thus involvement of different signaling mediators.

The effect of inhibitors of phosphatidylinositol-3-kinase-related kinases (PIKK): ataxia-telangiectasia mutated (ATM), ATM- and Rad3-related (ATR) and DNA-dependent protein kinase (DNA-PK) on response of HepG2 human liver cancer cells to benzo[a]pyrene (BaP) was investigated. PIKK inhibitors: KU55933 (5 μM), NU7026 (10 μM) or caffeine (1 and 2mM) when used as single agents or in combinations (KU55933/NU7026 and caffeine/NU7026) did not significantly influence the BaP (3 μM) cytotoxicity (MTT reduction test). BaP induced a weak proapoptotic effect which was moderately enhanced by both inhibitor combinations. HepG2 cells exposed to BaP showed a strong S-phase arrest which was considerably diminished by both inhibitor combinations. The DNA damage (comet assay) induced after continuous 24h exposure to BaP was significantly diminished by both inhibitor combinations. Weak induction of reactive oxygen species by BaP was observed, which was not modulated by the inhibitor combinations. Similarly, no modulation of the glutathione levels was observed.

Some reports indicate that the silver released from dermally applied products containing silver nanoparticles (AgNP) (e.g. wound dressings or cosmetics) can penetrate the skin, particularly if damaged. AgNP were also shown to have cytotoxic and genotoxic activity. In the present study percutaneous absorption of AgNP of two different nominal sizes (Ag15 nm or Ag45 nm by STEM) and surface modification, i.e. citrate or PEG stabilized nanoparticles, in combination with cosmetic ingredients, i.e. aluminum chloride (AlCl 3 ), methyl paraben (MPB), or di-n-butyl phthalate (DBPH) was assessed using in vitro model based on dermatomed pig skin. The inductively coupled plasma mass spectrometry (ICP-MS) measurements after 24 h in receptor fluid indicated low, but detectable silver absorption and no statistically significant differences in the penetration between the 4 types of AgNP studied at 47, 470 or 750 μg/ml. Similarly, no significant differences were observed for silver penetration when the AgNP were used in combinations with AlCl 3 (500 μM), MPB (1250 μM) or DBPH (35 μM). The measured highest amount of Ag that penetrated was 0.45 ng/cm 2 (0.365–0.974 ng/cm 2 ) for PEG stabilized Ag15 nm + MPB.