A 23-year-old previously healthy man comes to the office after noticing a painless, hard mass in the left testis. Scrotal ultrasound shows a solid testicular mass, and CT scan of the abdomen and pelvis shows left paraaortic lymphadenopathy. Left orchidectomy is performed and postoperative histopathology reveals seminoma of the testis. External beam radiotherapy is administered to the paraaortic metastatic area. Several weeks later, the retroperitoneal nodes are observed to have markedly decreased in size. Which of the following is the most likely effect of the therapy used on the metastatic cells in this patient?
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Therapeutic ionizing radiation (eg, gamma rays, x-rays), commonly used to treat or palliate several types of cancer, can cause cell death through 2 major mechanisms:
The effect of radiation is most pronounced in malignant cells as they are rapidly dividing and consequently less able to repair DNA damage. Epithelial surfaces (eg, bowel mucosa, skin) are also severely affected because they are rapidly dividing.
A characteristic cell death curve of exposure to radiation shows a nearly flat line on initial exposure, followed by a steep increase in cell death as the radiation dose increases (Diagram). The steep portion is due to a sharp increase in double-stranded DNA strand fractures and oxygen free radicals.
(Choice A) DNA methylation (only cytosine and adenine) typically inhibits gene transcription. Demethylation or hypomethylation of oncogenes (and hypermethylation of tumor suppressor genes) contributes to the development of some cancers.
(Choice B) DNA cross-linking can be induced by numerous chemical and physical agents, notably alkylating agents used in cancer treatment.
(Choice D) During DNA replication, incorrect base placement can occur, but enzymes scan the newly synthesized DNA strands for mismatched bases, which are then excised and replaced. This process is guided by the presence of adenine methylation (recognized by the enzymes) in the template strand, as the daughter strand remains unmethylated for some time following DNA replication.
(Choice E) DNA damage from exposure to ultraviolet radiation, a non-ionizing radiation, leads to the formation of pyrimidine-pyrimidine dimers (thymine dimers). Ionizing radiation has higher energy (enough to remove an electron), leading to more cell damage.
Educational objective:
Exposure to ionizing radiation, including therapeutic and palliative radiation therapy, induces DNA damage through DNA double-strand fractures and the formation of oxygen free radicals.