Modeling of dose-response relationships between Pb and Cd levels in testicular and prostate cancer tissues and testosterone levels

Dragana Javorac; Katarina  Baralić; Djurdjica  Marić; Evica  Antonijević Miljaković; Milena Andjelković; Marijana Ćurčić; Danijela Djukić-Ćosić; Zorica Bulat; Biljana Antonijević; Stefan  Mandić Rajčević; Miodrag  Aćimović; Aleksandra  Buha Djordjević

Dragana Javorac University of Belgrade – Faculty of Pharmacy, Department of Toxicology “Akademik Danilo Soldatović”
Katarina Baralić University of Belgrade – Faculty of Pharmacy, Department of Toxicology „Akademik Danilo Soldatović“
Djurdjica Marić University of Belgrade – Faculty of Pharmacy, Department of Toxicology „Akademik Danilo Soldatović“
Evica Antonijević Miljaković University of Belgrade – Faculty of Pharmacy, Department of Toxicology „Akademik Danilo Soldatović“
Milena Andjelković University of Belgrade – Faculty of Pharmacy, Department of Toxicology „Akademik Danilo Soldatović“; Health center Kosovska Mitrovica
Marijana Ćurčić University of Belgrade – Faculty of Pharmacy, Department of Toxicology „Akademik Danilo Soldatović“
Danijela Djukić-Ćosić University of Belgrade – Faculty of Pharmacy, Department of Toxicology „Akademik Danilo Soldatović“
Zorica Bulat University of Belgrade – Faculty of Pharmacy, Department of Toxicology „Akademik Danilo Soldatović“
Biljana Antonijević University of Belgrade – Faculty of Pharmacy, Department of Toxicology „Akademik Danilo Soldatović“
Stefan Mandić Rajčević University of Belgrade – Faculty of Medicine, Institute of Social Medicine and School of Public Health and Health Management
Miodrag Aćimović Clinical Center of Serbia, Urological Clinic
Aleksandra Buha Djordjević University of Belgrade – Faculty of Pharmacy, Department of Toxicology „Akademik Danilo Soldatović“

Abstract

Exposure to lead (Pb) and cadmium (Cd) poses risk to human health. It is known that these metals have toxic impact on male reproductive system, leading to physiological disorders and infertility. Limited data indicates the carcinogenic potential of Pb, while Cd has been recognized as carcinogen. Benchmark dose-effect modeling can be applied to data from human, animal and ecotoxicological studies with the aim to obtain Benchmark dose (BMD), starting point in human health risk assessment. The aim of this study was to use Benchmark modeling to determine the dose-effect relationship between Pb and Cd levels in tissues of testicular and prostate cancer patients and serum testosterone levels. The study was conducted at the Clinical Center of Serbia, and included 104 patients with prostate and testicular cancer. Cd and Pb levels (ng/g) were measured by atomic absorption spectrophotometry in isolated healthy surrounding and carcinoma-affected tissues. Testosterone levels (ng/mL) were measured using the chemiluminescence immunoassay (CLIA) method. Dose-effect modeling was performed using PROAST70.1 software with continuous data. The dose dependence was obtained between Cd levels in tumor tissue and testosterone levels (BMD: 0.0024 ng Cd/g, prostate cancer and 0.0038 ng Cd/g, testicular cancer). Dose dependence was obtained between Cd levels in healthy surrounding tissue and testosterone levels (BMD: 0.0092 ng Cd/g). No dose dependence was obtained when modeling Pb levels as a dose. The data from this study indicate a potential link between Cd and testosterone levels, i.e. potential association of Cd exposure with male reproductive health.