Tracing the movement of persistent organic pollutants at a high-mountain sampling site by chemometric assessment.

The main objective of the present study was to determine and differentiate the concentration levels, to define the probable sources of persistent organic pollutants (POPs) pollution in the atmospheric air and their seasonal variations in Bulgaria, on the high mountain peak Moussala, Rila Mountain. The study was based on the obtained results from the passive monitoring of POPs in 2014-2017. During this period, the measurements of POPs were performed with passive samplers, advanced instrumental methods analytically determined the concentrations of PAHs, and the analysis of the obtained data was performed by the multivariate statistical analysis (cluster, factor and time-series analysis). It is shown that the POPs species could be correctly classified according to their chemical nature into several patterns of similarity and their concentration profile depends on the annual season.

How can the natural radiation background affect DNA integrity in angiosperm plant species at different altitudes in Rila Mountain (Southwest Bulgaria)?

Climate changes and anthropogenic factors are the main factors contributing to the destruction of natural ecosystems. The aim of this study was to investigate the extent to which wild plants adapt to UV, gamma background, and gross beta activity, as well as the possible damage that can be recorded in plants growing at different altitudes in Rila Mountain. We used physicochemical, cytogenetic, and molecular methods. Our investigations were done on the nine plant species characteristic of the ecosystems in Rila Mountain at three altitudes: 1500 m, 1782 m, and 2925 m. The registered beta activity in the plants did not depend on the altitude of the habitats. Our results showed that wild plant species differ in their tolerance to the combined effect of UV and IR radiation as well as climate factors. The genotype plays a more important role than the difference in the habitat altitude. The comet assay adapted by us for these plant species showed that the DNA of Epilobium angustifolium L. (Onagraceae) growing at 1500 m was more susceptible to damage than that of Dactylis glomerata L. (Poaceae). Both these species growing at 1782 m did not show any increase in DNA damage evaluated as the level of DNA migration. The level of DNA damage in Pedicularis orthantha Griseb. (Orobanchaceae) at 2925 m was comparable to that at a lower altitude. Regarding the formation of micronuclei, grass species were more sensitive to UV- and IR-induced DNA damage than cereals. Our data imply the existence of specific protective mechanisms developed by plants to overcome DNA damage induced by stress factors.

A 99mTc-labeled gemcitabine bisphosphonate drug conjugate as a probe to assess the potential for targeted chemotherapy of metastatic bone cancer.

INTRODUCTION: A novel compound with the potential for "targeted" therapy for cancer patients was prepared using a conjugate between the potent anticancer drug Gemzar (gemcitabine) and a bisphosphonate. This conjugate would be expected to accumulate at sites of bone metastatic cancer by virtue of an affinity of the bisphosphonate for bone undergoing osteoclastic and osteoblastic remodeling. Release of the anticancer drug at the site of the tumor would provide high local concentrations of the drug but avoid systemic toxicity. METHODS: The conjugate was tested for bone binding by labeling with technetium-99m and using an in vitro test procedure with either purified hydroxyapatite (HA) or powdered bovine bone. Biodistribution and pharmacokinetic studies in mice were used to determine the excretion and bone-binding characteristics of the test compound. RESULTS AND CONCLUSIONS: The conjugate binds readily to powdered bone and HA using the in vitro test systems. In animal studies, the conjugate is found predominantly in bone with low soft tissue uptake after intravenous dosing. Unbound compound undergoes renal excretion. The gemcitabine bisphosphonate complex is a promising lead compound for investigation in metastatic bone cancer that may provide a therapeutic effect without undue toxicity.

Preclinical investigations of drug and radionuclide conjugates of bisphosphonates for the treatment of metastatic bone cancer.

The potential targeting of therapeutic bisphosphonate conjugates to bone metastatic lesions was evaluated in vivo in mice. A bisphosphonate conjugate with 5-fluorouracil was synthesized as a potential chemotherapy agent, and a bisphosphonate conjugate with diethylenetriaminepentaacetic acid (DTPA) was prepared as a potential carrier of cytotoxic radionuclides. The compounds are hypothesized to be able to deliver either high doses of radiation or a high concentration of chemotherapy agents at sites of increased osteoclastic activity in patients with bony metastases while exhibiting minimal toxicity to normal tissues. Tissue distribution studies with the 99mTc-labeled bisphosphonate conjugates with DTPA and 5-fluorouracil showed rapid blood clearance and excretion of unbound activity, clearance from most tissues, and substantial retention of the bisphosphonates in bone. For the DTPA conjugate, activity in the bone represents 13.6% of the total injected dose at 8 hours following injection, representing 54.3% of the total whole-body activity at this time period. Under the same conditions, the 5-fluorouracil conjugate showed a 17.1% bone uptake at 60.2% of the whole-body activity. This normal bone uptake predicts that high concentrations of conjugates are expected to be achieved at sites of bone metastatic disease. Chemotherapy and radiotherapy studies with these compounds in animal models of metastatic bone cancer are underway.