RESUMO
Male CBA mice received graded doses (450-750 rad) of total-body gamma-radiation (TBR) from a dual-beam 137Cs irradiator. Commencing directly after TBR, 2 days later, or 6 days later, groups of mice received supplemental vitamin A (Vit A) or beta-carotene (beta-Car), compounds previously found to reduce radiation disease in mice subjected to partial-body X-irradiation. Given directly after TBR, supplemental Vit A decreased mortality, evidenced by increases in the radiation dose required to kill 50% of the mice within 30 days (LD50/30). In one experiment, Vit A increased the LD50/30 from 555 to 620 rad; in another experiment, Vit A increased the dose from 505 to 630 rad. Similarly, in a third experiment, supplemental beta-Car increased the LD50/30 from 510 to 645 rad. Additionally, each compound increased the survival times, even of those mice that died within 30 days. In addition to reduction of mortality and prolongation of survival time, supplemental Vit A moderated weight loss, adrenal gland hyperemia, thymus involution, and lymphopenia--all signs of radiation toxicity. Delaying the supplementation for 2 days after irradiation did not greatly reduce the efficacy of Vit A; however, delaying supplementation for 6 days decreased its effect almost completely.
Assuntos
Glândulas Suprarrenais/efeitos da radiação , Carotenoides/farmacologia , Leucócitos/efeitos da radiação , Timo/efeitos da radiação , Vitamina A/farmacologia , Glândulas Suprarrenais/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Relação Dose-Resposta à Radiação , Raios gama , Leucócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos CBA , Timo/efeitos dos fármacos , Irradiação Corporal Total , beta CarotenoRESUMO
Male CBA/J mice, ingesting a vitamin A- and beta-carotene-sufficient laboratory chow, were inoculated in a hind limb with 2 X 10(5) C3HBA adenocarcinoma cells. When the mean tumor size was 6.2 mm, the mice were divided randomly into groups; some groups received supplemental vitamin A or beta-carotene, some received 3,000 rad local radiation to the tumor, and others received both radiation and one of the supplements. All mice that received only radiation or one of the dietary supplements died within 3 months. When local irradiation and supplemental vitamin A or beta-carotene were coupled, "complete" tumor regression occurred in every case (12/12), and tumor regrowth in and death of the mice occurred in only 1 of 12 in each of these groups during the succeeding 12 months. One year after irradiation and dietary supplementation, half the surviving mice were switched back to the control chow. During the next year, none of the mice remaining on the vitamin A or beta-carotene supplements developed tumors; however, of 6 mice switched from vitamin A, 5 had tumors that reappeared. In contrast, tumors recurred in only 2 of 6 mice after they were switched from beta-carotene. A second experiment yielded similar results. These results show that both vitamin A and beta-carotene supplementation added remarkably to the antitumor effect of local irradiation. beta-Carotene supplementation produced a greater residual antitumor action than vitamin A supplementation after the supplements were discontinued, which may have been due to greater tissue storage of beta-carotene.
Assuntos
Adenocarcinoma/radioterapia , Carotenoides/uso terapêutico , Vitamina A/uso terapêutico , Adenocarcinoma/tratamento farmacológico , Animais , Masculino , Camundongos , Camundongos Endogâmicos DBA , Camundongos Endogâmicos , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/radioterapia , Dosagem Radioterapêutica , Vitamina A/toxicidade , beta CarotenoRESUMO
Decreased tumor incidence, increased latent period, and increased survival time were observed in C3H/HeJ mice fed supplemental beta-carotene for 3 days and then inoculated with 10(4) C3HBA (syngeneic) tumor cells. In addition, C3H/HeJ, C3H/He, and CBA/J mice, fed supplemental beta-carotene beginning immediately after they were inoculated with 2 X 10(5) C3HBA tumor cells, showed decreased tumor growth and increased survival time. When beta-carotene was fed to mice in which palpable tumors were already present, it similarly slowed tumor growth and extended animal survival time. Ascorbic acid supplementation (5 g/kg diet), introduced into the experiment as a possible synergist for beta-carotene's antitumor action, was without therapeutic action when tested in the presence or absence of beta-carotene supplements. The basal diet, a standard commercial mouse chow, contains more vitamin A than the National Research Council's recommended dietary allowance for normal rodents and supports normal growth, reproduction, and longevity of normal mice. The work reported here is the first demonstration of the antitumor action of beta-carotene in animals with a transplanted tumor.
Assuntos
Adenocarcinoma/tratamento farmacológico , Ácido Ascórbico/uso terapêutico , Carotenoides/uso terapêutico , Animais , Osso e Ossos/efeitos dos fármacos , Dieta , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos CBA , Transplante de Neoplasias , Vitamina A/toxicidadeRESUMO
We have previously reported that supplemental vitamin A ameliorates the stress response to a wide variety of noxious agents. The present study was carried out to determine how supplemental vitamin A influences the course of radiation sickness in C3H female mice subjected to 3000 R irradiation of one lower hind limb. All mice ingested a chow diet containing about 13,000 units of vitamin A/kg diet (about half as preformed vitamin A and half as beta-carotene) which supports normal growth, development, and reproduction of normal mice. One hundred fifty thousand units of vitamin A/kg chow was added for the vitamin A supplemented mice. All mice ate and drank ad libitum. The supplemental vitamin A feeding was begun either 3 days before radiation or immediately after radiation. There were no significant differences in the effects of these two regimens. The supplemental vitamin A prevented the weight loss, moderated the adrenal hypertrophy, prevented the thymic involution, and lessened the lymphopenia due to radiation. We conclude that supplemental vitamin A has both prophylactic and therapeutic benefits in radiation-induced disease.
Assuntos
Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação , Vitamina A/uso terapêutico , Glândulas Suprarrenais/patologia , Animais , Peso Corporal/efeitos da radiação , Feminino , Membro Posterior/efeitos da radiação , Contagem de Leucócitos , Camundongos , Camundongos Endogâmicos C3H , Tamanho do Órgão/efeitos dos fármacos , Linfócitos T/efeitos da radiação , Timo/patologiaRESUMO
Goodson and Hunt showed that wound healing is impaired in streptozotocin (Sz) diabetic rats; we speculated that this impairment results from defective early inflammatory responses to wounding. Because we had shown that supplemental vitamin A stimulates the early inflammatory response to wounding in nondiabetic rats, we studied the effect of supplemental vitamin A on wound healing in rats with Sz-induced diabetes. Male Sprague-Dawley rats were fed a commercial rat chow containing twice the amount of vitamin A recommended by the NRC for healthy rats. The rats ate and drank (tap water) ad libitum. Two-thirds of the rats were injected (intravenously) with Sz 60 mg/kg body weight. All of these rats became diabetic (hyperglycemia greater than 350 mg/dl, hyperphagic, polydipsic, polyuric, glycosuric greater than 2%). Seven days later, half of the Sz-injected rats were continued on the chow (Group 2) while the other half (Group 3) were switched to the chow supplemented with 150,000 units of vitamin A/kg chow. The next day, all were wounded (7 cm skin incisions and s.c. polyvinyl alcohol sponge implants). Similarly wounded saline injected nondiabetic rats ingesting the unsupplemented chow served as controls (Group 1). The wounds of Group 2 rats healed poorly compared to Group 1 (breaking strength of skin incisions, 308 +/- 19 g vs 584 +/- 23 g, p less than 0.001; hydroxyproline of the sponge reparative tissue, 0.87 mg vs 2.40 mg/100 mg sponge p less than 0.001). Supplemental vitamin A (Group 3) did not affect the hyperglycemia, hyperphagia, polydipsia or glycosuria, but increased the breaking strengths of the incisions of the diabetic rats (468 +/- 40 g, p less than 0.001), and the sponge hydroxyproline (2.38 mg/100 mg sponge, p less than 0.001). In another experiment, in which the wounding and start of supplemental vitamin A were delayed until 28 days after streptozotocin administration (50 mg/kg body weight), similar results were obtained. Streptozotocin diabetes also caused a decrease in the cross-linking of reparative collagen as judged by the ratio of breaking strengths of skin incisions before and after formalin fixation. Supplemental vitamin A did not influence this defect. Sz also caused peripheral lymphocytopenia, adrenal hypertrophy and thymic involution which responded to the supplemental vitamin A. Based upon experimental data and theoretical considerations we conclude Sz diabetes causes two defects in wound healing: a) quantitatively (reduction in reparative collagen accumulation) and b) qualitative reduction in the degree of cross-linking of reparative wound collagen. The action of supplemental vitamin A in correcting the impaired wound healing, adrenal enlargement, thymic involution and lymphocytopenia of Sz-diabetic rats is independent of an effect on their disturbed carbohydrate metabolism.