Objective ― impact of different time regimens of deuterium depletion on progression of syngeneic grafted tumor in mice was investigated. Material and Methods ― Experiment was performed on 64 C57Bl/6 mice divided into two groups with substitution of regular water for deuterium depleted water: 30 days prior to tumor cell inoculation and sinse the 1st day of inoculation. Mice taking destilled mineralized water were considered as a control group. Half of the mice were injected melanoma B16 cells subcutaneously for assessment of survival rate and tumor growth inhibition index. The other mice were intravenously injected melanoma cells for estimation of lung hematogenous metastasis. Results ― Deuterium depletion began at the day of tumor inoculation did not change the parameters of survival rate (38.83±7.69 days vs. 41.33±6.22days in the control). Tumor growth inhibition was found only at initial stage of tumor progression. Number of melanoma lung metastasis did not differ from the control values (32.30±6.12 and 28.33±5.38. consequently). The group of mice with preliminary consumption of deuterium depleted water demonstrated significantly higher survival rate (70.10±16.20 days), tumor inhibition index, and attenuation of lung metastasis (6.0±1.20). Conclusion ― Our findings demonstrate that deuterium depletion exerts antitumor effect by both inhibition of tumor growth and metastasis, but development of the effect is time-dependent.
Dichlorodiphenyltrichloroethane (DDT) is the most widespread, persistent pollutant and endocrine disruptor on the planet. Although DDT has been found to block androgen receptors, the effects of its low-dose exposure in different periods of ontogeny on the male reproductive system remain unclear. We evaluate sex steroid hormone production in the pubertal period and after maturation in male Wistar rats exposed to low doses of o,p’-DDT, either during prenatal and postnatal development or postnatal development alone. Prenatally and postnatally exposed rats exhibit lower testosterone production and increased estradiol and estriol serum levels after maturation, associated with the delayed growth of gonads. Postnatally exposed rats demonstrate accelerated growth of gonads and higher testosterone production in the pubertal period. In contrast to the previous group, they do not present raised estradiol production. All of the exposed animals exhibit a reduced conversion of progesterone to 17OH-progesterone after sexual maturation, which indicates putative attenuation of sex steroid production. Thus, the study reveals age-dependent outcomes of low-dose exposure to DDT. Prenatal onset of exposure results in the later onset of androgen production and the enhanced conversion of androgens to estrogens after puberty, while postnatal exposure induces the earlier onset of androgen secretion.
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