Induction of Sperm Head Abnormalities by Incorporated Radionuclides: Dependence on Subcellular Distribution, Type of Radiation, Dose Rate, and Presence of Radioprotectors

Abstract

In contrast to the biological effects caused by exposure to external beams of radiation, the effects of tissue-incorporated radionuclides are highly dependent on the type of radiation emitted and on their distribution at the macroscopic, microscopic, and subcellular levels, which are in turn determined by the chemical nature of the radionuclides administered. Induction of abnormalities of sperm heads in mice is investigated in this work after the injection of a variety of radiochemicals including α emitters. When the initial slopes of the dose-response curves are used to compare the relative biological effectiveness (RBE) of different radiocompounds, the α particles emitted in the decay of 210 Po are more effective than Auger electrons emitted by 125 I incorporated in the DNA of the spermatogonial cells, and both emissions are more effective than X rays. It is also shown that the Auger emitters ( 125 I, 111 In) distributed in the cell nucleus are more efficient in producing abnormalities than the same radionuclides localized in the cytoplasm. These findings are consistent with our earlier observations, where spermatogonial cell survival is assayed as a function of the testicular absorbed dose. Further, chronic irradiation of testis with γ rays from intratesticularly administered 7 Be is about three times more effective in causing abnormalities than a single acute exposure to 120-kVp X rays. The resulting RBE values correlate well with our data on sperm head survival with the same radiocompounds. Finally, the radioprotector cysteamine, when administered in small, nontoxic amounts, significantly reduces the incidence of sperm abnormalities from α-particle radiation as well as emissions from 125 I incorporated into DNA, the dose reduction factors being 10 and 14, respectively.

Radiotoxicity of Gadolinium-148 and Radium-223 in Mouse Testes: Relative Biological Effectiveness of Alpha-Particle Emitters In Vivo

“…This same model was used in our earlier reports on the biological effects of α-particle emitters (5) and other radionuclides (6)(7)(8)(9)(10)(11). The process of spermatogenesis in mouse and man is very similar, except for the time scale: about 5 weeks for mouse and 10 weeks for man (12,13).…”

“…Therefore, particular attention must be paid to the selection of the reference radiation (5,10,16,30). In our earlier work using the same experimental model, the effects of a variety of sources of low-LET radiation were examined including external X rays (8) and intratesticularly administered β-particle and γ-ray emitters (8,16,24).…”

“…As in our earlier work (7,9,10), the radiochemicals were injected intratesticularly along the long axis of the right testis (standard 3 μl volume) of mice anesthetized with ether. The needle was slowly withdrawn from the organ during the injection to facilitate a reasonably uniform distribution of activity in the organ.…”

“…The testicular absorbed dose from the radionuclides was calculated as described previously (5,(7)(8)(9)(10). Briefly, the mean testicular absorbed dose D is given by (26) (2) where the cumulated activity à is the time integral of the activity in the organ ∫A(t)dt, Δ is the mean energy emitted per nuclear transition, φ is the absorbed fraction, m is the average mass of the testis (0.1 g), and i denotes the ith radiation component emitted by the radionuclide.…”

A Small-Scale Anatomic Model for Testicular Radiation Dosimetry for Radionuclides Localized in the Human Testes

“…The radiobiologic response of testicular cells undergoing spermatogenesis to ionizing radiation has been well established in the mouse and rat (13)(14)(15) and is considered to be relevant to humans (16). Radiation damage and the death of germ cells can impair fertility in a dose-dependent way.…”