title: Suppression of the later stages of radiation-induced carcinogenesis by antioxidant dietary formulations.
abstract: We have previously reported data from a long-term carcinogenesis study indicating that dietary antioxidant supplements can suppress radiation-induced malignant lymphoma and harderian gland tumors induced by space radiations (specifically, 1 GeV/n iron ions or protons) in CBA/J mice. Two different antioxidant dietary supplements were used in these studies: a supplement containing a mixture of antioxidant agents [l-selenomethionine (SeM), N-acetyl cysteine (NAC), ascorbic acid, co-enzyme Q10, α-lipoic acid and vitamin E succinate], termed the AOX supplement, and another supplement known as Bowman-Birk Inhibitor Concentrate (BBIC). In the present report, the results from the earlier analysis of the harderian gland data from the published long-term animal study have been combined with new data derived from the same long-term animal study. In the earlier analysis, harderian glands were removed from animals exhibiting abnormalities (e.g. visibly swollen areas) around the eyes at the time of euthanasia or death in the long-term animal study. Abnormalities around the eyes were usually due to the development of tumors in the harderian glands of these mice. The new data presented here focused on the histopathological results obtained from analyses of the harderian glands of mice that did not have visible abnormalities around the eyes at the time of necropsy in the long-term animal study. In this paper, the original published data and the new data have been combined to provide a more complete evaluation of the harderian glands from animals in the long-term carcinogenesis study, with all available harderian glands from the animals processed and prepared for histopathological evaluation. The results indicate that, although dietary antioxidant supplements suppressed harderian gland tumors in a statistically significant fashion when all glands were analyzed, the antioxidant diets were less effective at suppressing the incidence of all harderian gland tumors than they were at suppressing the incidence of large harderian gland tumors (>2 mm) observed at animal necropsy. These results suggest that the dietary antioxidant formulations had major suppressive effects in the later stages of radiation-induced carcinogenesis in vivo. It is hypothesized that the dietary antioxidant formulations prevented the early-stage neoplastic growths from progressing to fully developed, malignant tumors. In addition, the antioxidant dietary formulations were very effective at preventing the development of proton- or iron-ion-induced malignant tumors, because, in contrast to irradiated controls, no malignant tumors were observed in the irradiated animals maintained on either of the dietary antioxidant diets.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6072, USA. akennedy@mail.med.upenn.edu
authors.forename: Ann R
authors.initials: AR
authors.lastname: Kennedy
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Ware
authors.forename: William
authors.initials: W
authors.lastname: Carlton
authors.forename: James G
authors.initials: JG
authors.lastname: Davis
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use*; D019587:Dietary Supplements; D006243:Harderian Gland / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D008297:Male; D051379:Mice; D009367:Neoplasm Staging; D009381:Neoplasms, Radiation-Induced / Q000178:diet therapy* / Q000473:pathology*
chemical_list: D000975:Antioxidants