RESUMO
Meal timing can reset circadian clocks in peripheral tissues. We investigated the effects of such non-photic entrainment on tumor growth rate. Two experiments involved a total of 61 male B6D2F(1) mice synchronized with an alternation of 12 h of light (L) and 12 h of darkness (D) (LD12:12). Mice were randomly allocated to have access to food ad libitum, or restricted to 4 or 6 h during L or D. Rest-activity and body temperature, two circadian outputs, were monitored with an intra-peritoneal sensor. Glasgow osteosarcoma was inoculated into both flanks of each mouse ten days after meal timing onset. Before tumor inoculation, meal timing during D amplified the 24-h rhythms in rest-activity and body temperature with minimal phase alteration as compared to ad libitum feeding. Conversely, meal timing during L induced dominant 12-h or 8-h rhythmic components in activity, nearly doubled the 24-h amplitude of body temperature and shifted its acrophase (time of maximum) from approximately mid-D to approximately mid-L. Thirteen days after tumor inoculation, mean tumor weight (+/- SEM, mg) was 1503 +/- 150 in ad libitum mice, 1077 +/- 157 in mice fed during D and 577 +/- 139 in mice fed during L (ANOVA, p < 0.0001). Overall survival was prolonged in the mice fed during L (median, 17.5 days, d) as compared with those fed during D (14.5 d) or ad libitum (14 d) (Log Rank, p = 0.0035). The internal desynchronization produced by meal timing during L slowed down tumor progression, an effect possibly resulting from improved host-mediated tumor control and/or altered tumor circadian clocks.
Assuntos
Neoplasias Ósseas/patologia , Comportamento Alimentar , Osteossarcoma/patologia , Animais , Temperatura Corporal/fisiologia , Ritmo Circadiano , Progressão da Doença , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Atividade Motora/fisiologia , Transplante de Neoplasias , Taxa de SobrevidaRESUMO
AIM: To study the effect of mitoxantrone (Mit) on DNA polymerases of tumor cells. METHODS: DNA polymerases of Ehrlich ascites carcinoma cells were isolated by phosphocellulose column chromatography. The effects of Mit on DNA polymerase alpha, beta, and gamma were detected by method of K Ono. RESULTS: Mit inhibited DNA polymerase alpha, beta, and gamma, IC50 values were 11.9, 6.5, and 11.9 mumol.L-1, and Ki 1.86, 2.22, and 2.05 mumol.L-1, respectively. The inhibitory mode of Mit on DNA polymerase alpha, beta, and gamma was competitive. CONCLUSION: Mit is a strong inhibitor on DNA polymerase alpha, beta, and gamma. The inhibitory mode was competition with respect to template DNA.