Role of ornithine decarboxylase in diallyl sulfide inhibition of colonic radiation injury in the mouse.
Diallyl sulfide (DAS), a major flavor component of garlic (Allium sativum) that has previously been shown to inhibit colon carcinogenesis in experimental animals, was investigated for its ability to reduce acute colonic mucosal injury following gamma-ray exposure. Female C57BL/6J mice received either vehicle or DAS (200 mg/kg) by gavage 3 h prior to a single, whole body dose of radiation from a 60Co source. After 24 h, animals were killed and their colons were excised, fixed, and sectioned. DAS significantly inhibited nuclear aberration formation (a measure of nuclear damage) over a radiation dose range of 0.5 to 10 Gy. The degree of protection was related to the dose of DAS and the compound was ineffective if given after irradiation. Following 6 Gy, both DNA synthesis in vivo (measured by [3H]thymidine incorporation into DNA) and the activity of ornithine decarboxylase (an important regulator of DNA synthesis) were elevated for more than 14 days. The induction of both these parameters was significantly suppressed by administering DAS prior to radiation exposure. To determine the role of polyamine synthesis in affecting the severity of radiation damage in the large intestine, difluoromethylornithine, an ornithine decarboxylase inhibitor, was administered in the drinking water of the animals 24 h prior to and following radiation treatment. Difluoromethylornithine abolished the ability of DAS to reduce colonic nuclear damage caused by radiation exposure. Thus DAS protects against colonic radiation injury via a polyamine-dependent pathway.
Baer
A R
AR
Section of Gastrointestinal Oncology and Digestive Diseases, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Wargovich
M J
MJ
D000498:Allyl Compounds; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000528:radiation effects; D003106:Colon / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects*; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D000518:Eflornithine / Q000494:pharmacology; D005260:Female; D005737:Garlic; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010946:Plants, Medicinal; D011832:Radiation Injuries / Q000517:prevention & control*; D013440:Sulfides / Q000494:pharmacology / Q000627:therapeutic use*
D000498:Allyl Compounds; D013440:Sulfides; C038491:allyl sulfide; D009955:Ornithine Decarboxylase; D000518:Eflornithine