RESUMEN
BACKGROUND: The incidence of cutaneous malignant melanoma (CMM) and melanoma in situ (MIS) has been increasing during the last 50 years. Malignant melanoma (MM) is also the most common intraocular malignancy (IMM). Besides ultraviolet radiation, the cause of these tumours is largely unknown. OBJECTIVES: We designed a study to examine the effect of body mass index (BMI) and tobacco use on the risk for MM and MIS. METHODS: Analyses were performed on a nationwide cohort of 339 802 Swedish construction workers. Exposure information was collected prospectively by questionnaires combined with personal interviews. RESULTS: Follow up yielded a total of 7 663 400 person-years during which 1639 workers developed MM/MIS. The risk for MM/MIS was reduced in current or previous smokers compared with those who had never smoked, both when analysing all smoking tobacco products combined and when analysing cigarette and pipe smokers separately. The risk was further diminished with longer duration of smoking and greater quantity of tobacco smoked. The effect was more evident in CMM/MIS than in IMM. Snuff taking conferred a decreased risk for CMM/MIS, and a BMI over normal weight range conferred an increased risk for CMM. CONCLUSIONS: Tobacco smoking was found to be inversely associated with the risk for CMM and MIS. The mechanism of action is unknown but it has been suggested to be due to the immune suppressive effect that tobacco exerts which would be protective against deleterious immune reactions caused by, for example, the sun. Neither is the mechanism behind the higher risk for CMM due to being overweight known. One hypothesis is that it is an effect of a hormonal imbalance. Further studies are required to elucidate these mechanisms.
Asunto(s)
Índice de Masa Corporal , Neoplasias del Ojo/etiología , Melanoma/etiología , Neoplasias Cutáneas/etiología , Fumar/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Estudios Transversales , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Suecia/epidemiologíaRESUMEN
We investigated whether tobacco use causes cutaneous squamous cell carcinoma (CSCC) in a large cohort study with complete and long-term follow-up. A total of 756 incident cases occurred in a cohort of 337,311 men during a 30-year follow-up period, but no association was found between any kind of smoking tobacco use and CSCC risk, nor any risk change with increasing dose, duration or time since smoking cessation. Snuff use was associated with a decreased risk of CSCC. Overall, our study provides no evidence that tobacco use increases the risk of CSCC.
Asunto(s)
Carcinoma de Células Escamosas/etiología , Neoplasias Cutáneas/etiología , Fumar/efectos adversos , Tabaco sin Humo/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Carcinoma de Células Escamosas/epidemiología , Estudios de Cohortes , Estudios Epidemiológicos , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Neoplasias Cutáneas/epidemiología , Suecia/epidemiología , Factores de TiempoRESUMEN
Triethyl lead chloride (TEL) was added directly to female rat liver microsomal fractions at final concentrations of 0.0, 0.005, 0.05 and 0.5 mM, respectively. The effect of oestradiol on liver microsomal metabolism was studied in vitro by incubating the microsomes with radioactive oestradiol-17 beta. The oestradiol metabolites were separated, identified and quantified. The highest treatment concentrations resulted in decreased activities of enzymes that metabolize oestradiol-17 beta.
Asunto(s)
Estradiol/metabolismo , Microsomas Hepáticos/metabolismo , Compuestos Organometálicos/toxicidad , Animales , Sistema Enzimático del Citocromo P-450/análisis , Femenino , Hemoglobinas/metabolismo , Hidroxilación , Técnicas In Vitro , Compuestos Organometálicos/metabolismo , Ratas , Ratas EndogámicasRESUMEN
Female mice were injected intraperitoneally daily from day 18 of gestation and throughout lactation with triethyl lead chloride (TEL; 0.0, 0.5 and 1.0 mg/kg body wt). Off-spring of treated mothers displayed a slight perinatal growth retardation. Male off-spring appeared to be more sensitive to TEL, as indicated by their lower body weights. During the latter half of the lactation period the treated sucklings grew faster than controls, thereby compensating for their initially retarded growth, by the time of weaning. The hepatic cytochrome P-450 content of 9 to 10-day old sucklings of treated mothers was lower than in corresponding controls. We suggest that perinatal growth retardation is initiated by a disturbance in the uterus, e.g. reduced nutrient transport across the placenta.
Asunto(s)
Animales Recién Nacidos/crecimiento & desarrollo , Feto/efectos de los fármacos , Compuestos Organometálicos/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/análisis , Femenino , Retardo del Crecimiento Fetal/inducido químicamente , Intercambio Materno-Fetal/efectos de los fármacos , Ratones , EmbarazoRESUMEN
Triethyllead chloride was added directly to male rat liver microsomes (0.0, 0.05, 0.25, 0.5, 1.0, and 3.0 mM), or the rats were pretreated with ip injections, once a day for 2 days (0.0, 1.5, and 3.0 mg triethyllead chloride/kg body wt), and microsomes prepared without any further treatment on Day 3. The effects of these treatments on microsomal N-oxygenation and C-oxygenation in vitro were studied by using N-oxide formation and N-demethylation of N,N-dimethylaniline (DMA) as test reactions. Increased microsomal N-oxygenation was obtained by in vivo treatment and decreased microsomal C-oxygenation by in vitro treatment. As a result, either treatment thus gave rise to an increase in the N-oxygenation/C-oxygenation ratio. Conditions favoring accumulation of the N-oxide product may potentiate the tumor-inducing characteristics of carcinogenic aromatic amines.
Asunto(s)
Compuestos de Anilina/metabolismo , Plomo/farmacología , Microsomas Hepáticos/efectos de los fármacos , Compuestos Organometálicos/farmacología , Animales , Sistema Enzimático del Citocromo P-450/metabolismo , Masculino , Microsomas Hepáticos/metabolismo , NADH Deshidrogenasa/metabolismo , Nitrógeno/metabolismo , Oxígeno/metabolismo , Ratas , Ratas EndogámicasRESUMEN
In order to study the effect of organolead on the placental transfer of amino acids, triethyl lead chloride was administered by i.p. injections to pregnant guinea-pigs. The following day, the fetal part of the placenta was perfused in situ during i.v. infusion of alpha-aminoisobutyric acid (AIB) to the dam. It was found that triethyl lead treatment (2.5 mg/kg body wt) decreased the AIB-concentration in perfusion media compared with that of the control group. Treatment with 1 mg/kg body wt has no effect. It was also shown that the placental uptake of AIB in animals receiving 2.5 mg/kg body wt is significantly reduced compared with that of the control group. No such effect was obtained in animals receiving 1 mg/kg body wt. It is suggested that triethyl lead may inhibit placental Na+-K+-adenosinetriphosphatase, an enzyme involved with placental amino acid transport. Another possible explanation is a reduction in maternal placental blood flow.