Asunto(s)
Antineoplásicos/uso terapéutico , Hidrazinas/uso terapéutico , Leucemia L1210/tratamiento farmacológico , Urea/uso terapéutico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/toxicidad , Citarabina/uso terapéutico , Sinergismo Farmacológico , Femenino , Inyecciones Intraperitoneales , Inyecciones Subcutáneas , Masculino , Ratones , Factores de TiempoAsunto(s)
Antibacterianos/toxicidad , Nucleósidos/toxicidad , Animales , Aspartato Aminotransferasas/sangre , Conductos Biliares Intrahepáticos/efectos de los fármacos , Conductos Biliares Intrahepáticos/patología , Glucemia/análisis , Nitrógeno de la Urea Sanguínea , Enfermedad Hepática Inducida por Sustancias y Drogas , Sistema Digestivo/efectos de los fármacos , Perros , Femenino , Corazón/efectos de los fármacos , Necrosis de la Corteza Renal/complicaciones , Hígado/efectos de los fármacos , Hepatopatías/patología , Sistema Linfático/efectos de los fármacos , Masculino , Ratones , Miocardio/patología , Necrosis , Nucleósidos/administración & dosificación , Neumonía/inducido químicamente , Tiempo de Protrombina , Edema Pulmonar/inducido químicamente , RatasAsunto(s)
Antineoplásicos/toxicidad , Hidrazinas/toxicidad , Parálisis/inducido químicamente , Urea/toxicidad , Alopecia/inducido químicamente , Animales , Antineoplásicos/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Perros , Erupciones por Medicamentos/etiología , Guanina/administración & dosificación , Haplorrinos , Hipoglucemia/inducido químicamente , Inyecciones Intravenosas , Leucemia Experimental/tratamiento farmacológico , Ratones , Conejos , Ratas , Urea/administración & dosificaciónRESUMEN
Effects of beta-naphthoflavone (beta NF) on the activity of hepatic microsomal aflatoxin B1 (AFB1)-4-hydroxylase - the cytochrome P-450-dependent enzyme system which catalyzes the metabolism of AFB1 to AFM1 - and on AFB1-induced in vivo hepatocarcinogenesis were investigated in weanling male Fischer rats. A single i.p. injection of beta NF in doses of 20 mg/kg and 150 mg/kg induced AFB1-4-hydroxylase 3- and 4-fold, respectively, 48 h post injection. Feeding of diet containing 0.01% beta NF for a period of 9-weeks induced AFB1-4-hydroxylase approximately 2-fold. AFB1, given by intubation in a dose of 25 micrograms five times/week for 8 weeks, produced 42 weeks later a 100% incidence of liver lesions (neoplastic foci, nodules or tumors), but feeding beta-NF in diet at a concentration of 0.015% for one week prior to and during the 8 weeks of AFB1 treatment inhibited AFB1 hepatocarcinogenesis by approximately 75%. These results are in accord with the suggestion that AFB1-4-hydroxylase induction may be associated with the inhibition of AFB1 carcinogenesis, possibly occurring as a consequence of accelerated detoxification of AFB1 via its conversion to AFM1.
Asunto(s)
Aflatoxinas/toxicidad , Benzoflavonas/farmacología , Flavonoides/farmacología , Neoplasias Hepáticas Experimentales/prevención & control , Aflatoxina B1 , Aflatoxinas/metabolismo , Animales , Sistema Enzimático del Citocromo P-450/biosíntesis , Dieta , Inducción Enzimática/efectos de los fármacos , Inactivación Metabólica , Neoplasias Hepáticas Experimentales/inducido químicamente , Masculino , Ratas , Ratas Endogámicas F344 , Verduras , beta-naftoflavonaRESUMEN
Human placental microsomes isolated from term placentas derived from nonsmoking women and women smoking 1 to 40 cigarettes a day were analyzed for the metabolism of benzo(a)pyrene measured as various metabolites by HPLC and/or as aryl hydrocarbon hydroxylase (AHH)6 activity. In accordance with other reports, AHH activity was several times higher in smokers than in nonsmokers. Regression analysis on 13 different placental tissues from women smoking from 1 to 40 cigarettes demonstrated a high correlation (r = 0.8 to 0.9) between AHH activity (or the formation of benzo(a)pyrene phenols resolved by HPLC) versus the formation of the procarcinogenic benzo(a)pyrene-7,8-diol. Subsequent studies on placentas derived from 67 women who smoked 10 to 40 cigarettes per day demonstrated a definite dose-response relationship between AHH activity and the number of cigarettes smoked/day. The dose-response curve was sigmoidal in shape; however, when the data were plotted on a semi-log scale the curve assumed a linear shape, reaching saturation of AHH induction beyond 20 to 25 cigarettes/day. While mean AHH activity was dependent upon the number of cigarettes smoked/day, considerable interindividual variability in AHH (ranging more than 1,000-fold in some cases) was observed among individuals with comparable smoking histories, i.e. smoking the same number of cigarettes. Population distribution suggested clustering of the population in the low-AHH-activity region while cord-blood thiocyanate analysis and twin studies suggested that genetic factors contributed to a major portion of the inter-individual variability in AHH activity observed among smokers.