Journal of Applied Toxicology

The commonly held assumption that rodent mammary tumors resulting from elevated prolactin are species-specific, or not biologically relevant to humans, is incorrect. Substantial epidemiological, clinical and biological evidence now exists confirming the role of prolactin in human breast cancer. This evidence is evaluated and the argument presented that the tumorigenic risk from prolactin is therefore not species-specific to rodents but directly applies to humans. Further, as the mechanisms of prolactin-induced mammary tumor promotion and development appear analogous between rodents and humans, mammary tumorigenic findings in rodent carcinogenicity bioassays are both predictive and biologically relevant to the human response. Toxicologists and regulators need to consider this in carcinogenicity risk assessments.

Nanostructural materials have found a large number of applications in nanomedicine, from drug/gene delivery, cancer research, tissue engineering or bio-sensors. The surface, morphological, and structural properties of the nanoparticles are the major factors that control their specific behavior in biological environments and dictate their particular use as active agents for various applications in biology and medicine. This review looks at some of the most important aspects of using nanomaterials for cancer nanomedicine applications.

Cadmium exposure (0.25 and 1 mg/kg, i.p., 10 days) reduced body weight of rats and Zn mitigated this effect. Moreover, Cd increased Zn and Cd in liver tissue, which was not modified by Zn (2 mg/kg, i.p.). Zinc and/or Cd increased hepatic delta-ALA-D. However, only Cd (1mg/kg) induced metallothionein (MT), which was blocked by Zn. Thus, modulation of these two molecular endpoints of Cd toxicity was distinct

Vanadium, a transition metal released into the atmosphere as air-suspended particles, results from the combustion of fossil fuels. Suspended particles induce thrombosis and cardiovascular events as a result of oxide-reduction processes. HUVECs exposed to vanadium showed an increase in ROS and NO production. A decrease in cell proliferation, severe morphological changes and HUVEC apoptosis was also observed. Endothelial damage might be the epiphenomenon associated with the cardiovascular morbidity and mortality observed in individuals living in highly air-polluted areas.

It was observed that low lifetime female rats' exposure to cadmium disturbed the mineral status of the femur and tibia resulting in osteopenia or osteoporosis, and enhanced bone fragility. The findings seem to confirm the hypothesis that a low chronic exposure to cadmium may be a risk factor for osteoporosis and fractures of long bones in elderly women and indicate that greater attention should be paid to this toxic metal as an environmental risk factor for osteoporosis and fractures.

The model organism Caenorhabditis elegans has been used to compare the effects of synthetic polycyclic aromatic hydrocarbons (PAHs) with that of extractable organic matter (EOM) from environmental mixtures. In presence of EOM the expression level of some crucial genes indicated the activation of a stress–response mechanism. The exposure of C. elegans to the synthetic PAH mixtures, instead, determined the silencing of the transcriptional machinery, preventing the synthesis of proteins important for both the DNA-damage repair and the nematode survival.

To evaluate the effects of acetyl salicylic acid (ASA) and ibuprofen (IBP) on experimental liver fibrosis induced by CCl₄, we formed experimental groups of rats including vehicle and drug controls. Both drugs inhibited COX-2 activity, prevented oxidative stress; ASA inhibited partially and IBP totally increased TGF-β expression and collagen content. ASA and IBP prevented nuclear translocation of NFκB and, interestingly, ASA induced MMP-2 and MMP-13 whereas IBP induced MMP-2, MMP-9 and MMP-13.

To investigate the safety profile of a newly developed CpG ODN, CpG 684, we conducted a 28-day repeated dose toxicity study in rats. CpG 684 evaluated up-regulated the expressions of CD40 and CD86 molecules, induced cell hyperplasia in white pulp of spleen, and caused inflammatory cell infiltration and hyperplasia of fibrous tissue at injection sites. CpG 684 at 150 µg per rat increased the monocyte numbers and spleen weights, and led to the decrease in peripheral lymphocyte and some changes in serum chemistry.

Mutagenicity and transformation activity of three rare metal oxides and one elemental metal, In₂O₃, Dy₂O₃, WO₃ and Mo, were evaluated with respect to their chemical components and size dependency. The Ames test revealed that nano-sized Dy₂O₃, In₂O₃ and WO₃ possessed mutagenic potential for tumor initiation. From the results of transformation assays, In₂O₃ and Dy₂O₃ also showed potential ability for tumor promotion, although the particle size of these rare metal oxides did not affect their transformation activity.