TY - JOUR
T1 - Role of Ornithine Decarboxylase in Diallyl Sulfide Inhibition of Colonic Radiation Injury in the Mouse
AU - Baer, Allan R.
AU - Wargovich, Michael J.
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1989/9/15
Y1 - 1989/9/15
N2 - 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 γ-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 “Co 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 [3HJthymidine 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.
AB - 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 γ-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 “Co 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 [3HJthymidine 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.
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M3 - Article
C2 - 2504484
AN - SCOPUS:0024421668
VL - 49
SP - 5073
EP - 5076
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 18
ER -