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Andrea Baccarelli

Publications and source records attributed to Andrea Baccarelli.

25 records · Page 2Linked to original sources
PubMed2003

TCDD-mediated alterations in the AhR-dependent pathway in Seveso, Italy, 20 years after the accident.

Approximately 20 years after the Seveso, Italy, accident we conducted a population-based study to evaluate the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on cancer using mechanistically based biomarkers of dioxin response in humans. TCDD toxic effects are mediated by the aryl hydrocarbon receptor (AhR). We studied the AhR-dependent pathway in lymphocytes from 62 subjects randomly sampled from the highest exposed zones and 59 subjects from the surrounding non-contaminated area, frequency matched for age, gender and smoking. To our knowledge, this is the most comprehensive investigation to date designed to evaluate the key genes in the pathway, including AhR, aryl hydrocarbon receptor nuclear translocator, CYP1A1 and CYP1B1 transcripts and CYP1A1-associated 7-ethoxyresorufin O-deethylase (EROD) activity in a population heavily exposed to dioxin. Current lipid-adjusted plasma TCDD concentrations in these subjects ranged from 3.5 to 90 ng/kg (or p.p.t.) and were negatively associated with AhR mRNA in unstimulated peripheral blood mononuclear cells (P = 0.03). When mitogen-induced lymphocytes were cultured with 10 nM TCDD, all AhR-dependent genes were induced 1.2- to 13-fold. In these cells, plasma TCDD was associated with decreased EROD activity. In addition, there was a strong positive correlation between AhR and CYP1A1 expression (P = 0.001) and between AhR and CYP1B1 expression (P = 0.006). CYP1A1 expression was also strongly correlated with EROD activity (P = 0.001). The analysis of the expression of dioxin-inducible genes involved in carcinogenesis may help in determining dose-response relationships for human exposure to dioxin in vivo and in assessing the variability of human response, which may indicate the presence of subjects more susceptible to disease as a result of such exposures.

Aryl Hydrocarbon Hydroxylases↗
PubMed2003

Short- and long-term morbidity and mortality in the population exposed to dioxin after the "Seveso accident".

The early effects of 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) exposure in the population involved in the Seveso, Italy, incident in 1976, have been examined in numerous studies. Chloracne was the only effect linked with sufficient certainty to dioxin exposure. The possible long-term consequences were investigated with mortality and cancer incidence studies. Mortality and morbidity findings during the 20-year period following the accident showed increased risk from lymphoemopoietic neoplasm, digestive system cancer (rectum in males, and biliary tract among females, in particular) and respiratory system cancer (lung, among males). In the incidence analyses, also thyroid gland and pleura cancer appeared suggestively increased. Soft tissue sarcomas showed an increase in the largest, yet least exposed, exposure sub-cohort. Several hypotheses associating non-cancer effects with dioxin exposure were corroborated by findings in the Seveso population: this was the case with cardiovascular effects (possibly linked to both chemical exposure and stressful disaster experience), endocrine effects (diabetes among females) and reproductive effects: exposure of men to TCDD was linked to a lowered male/female sex ratio in their offspring. The results of many Seveso studies point to possible gender effects, in accordance with animal models. Notwithstanding the acknowledged study limitations (lack of individual exposure markers, short latency, and small population size for certain cancer types), results of previous experimental and epidemiological studies, along with mechanistic knowledge on dioxin toxicity, support the hypotheses that the observed excesses might be associated with dioxin exposure. The mortality and cancer incidence follow-up of the Seveso cohort are continuing.

Dioxins↗
PubMed2002

DNA repair, dysplastic nevi, and sunlight sensitivity in the development of cutaneous malignant melanoma.

BACKGROUND: Exposure to UV radiation is associated with cutaneous malignant melanoma (CMM). In mammalian cells, UV radiation induces DNA damage that can be repaired by the nucleotide excision repair system. We designed this case-control study to determine whether DNA repair capacity (DRC) is associated with the risk of CMM and to identify risk factors that may interact biologically with DRC in the development of melanoma. METHODS: Global DRC was measured in lymphocytes with the host-cell reactivation assay. Data were analyzed by use of multiple regression models. All statistical tests were two-sided. RESULTS: DRC could be determined for 132 case patients with incident melanoma and for 145 age- and sex-matched control subjects. No statistically significant association between melanoma risk and DRC by itself was found (odds ratio [OR] = 1.0; 95% confidence interval [CI] = 0.6 to 1.7, adjusted for age, sex, lymphocyte viability, and sample storage time). DRC, however, strongly influenced CMM risk in individuals with a low tanning ability or dysplastic nevi. Individuals with a low tanning ability and a low DRC had a higher risk for CMM (OR = 8.6; 95% CI = 2.7 to 27.5) than individuals with a higher tanning ability and a high DRC. Likewise, individuals with dysplastic nevi and a low DRC had a higher relative risk (OR = 6.7; 95% CI = 2.4 to 18.6) than those lacking dysplastic nevi and having a high DRC. Subjects with dysplastic nevi and a high DRC had an intermediate risk. A likelihood-ratio test gave statistically significant interactions between DRC and tanning response (P =.001) and between DRC and dysplastic nevus status (P =.04), which were independently associated with CMM risk. CONCLUSIONS: DRC may modify the risk for melanoma in the presence of other strong risk factors, such as a low tanning ability and the presence of dysplastic nevi. The occurrence of melanoma in subjects without these risk factors appears to be independent of DRC.

Adult↗
PubMed2002

Immunologic effects of dioxin: new results from Seveso and comparison with other studies.

Animal studies indicate that the immune system is one of the most sensitive targets of the toxic effects of 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD). TCDD inhibits immunoglobulin secretion and decreases resistance to bacterial, viral, and parasitic infections in exposed animals. Nearly 20 years after the Seveso, Italy, accident, we measured immunoglobulin and complement plasma levels in a random sample of the population in the most highly exposed zones (n = 62) and in the surrounding noncontaminated area (n = 58). Plasma IgG levels decreased with increasing TCDD plasma concentration (r = -0.35, p = 0.0002). Median IgG concentration decreased from 1,526 mg/dL in the group with the lowest (< 3.5 ppt) TCDD levels to 1,163 mg/dL in the group with the highest (20.1-89.9 ppt) TCDD levels (p = 0.002). The association was significant (p = 0.0004) after adjusting for age, sex, smoking, and consumption of domestic livestock and poultry in multiple regression analysis and persisted after exclusion of subjects with inflammatory diseases and those using antibiotics or nonsteroidal anti-inflammatory drugs. IgM, IgA, C3, and C4 plasma concentrations did not exhibit any consistent association with TCDD levels. We performed a systematic review of all the articles published between 1966 and 2001 on human subjects exposed to TCDD reporting information on circulating levels of immunoglobulins and/or complement components. The literature indicates that the evidence for effects of TCDD on humoral immunity is sparse. Methodologic issues, results, and possible sources of variation between studies are discussed. The possible long-term immunologic effects of TCDD exhibited by the participants of the present study, coupled with the increased incidence of lymphatic tumors in the area of the accident, warrant further investigation.

Accidents↗
PubMed2002

Long-term follow-up study of patients with adrenal incidentalomas.

BACKGROUND: The incidence of adrenal incidentalomas has sharply increased in recent decades and concurrent subtle endocrine abnormalities, or even subclinical conditions, have been identified. Nonetheless, data concerning possible changes in adrenal size and/or hormonal pattern during follow-up are still inadequate. OBJECTIVE: To evaluate long-term morphological and functional evolution of adrenal incidentalomas after initial diagnosis and to identify possible risk factors for hormonal hyperactivity and mass enlargement. PATIENTS: Sixty-four patients (34-79 years) were followed-up for 12-120 months (median 25.5 months). Initial computerized tomography scan showed a unilateral mass in 51 patients and bilateral lesions in 13 patients. Average mass diameter at diagnosis was 2.5+/-0.1 cm (range 1.0-4.0). Twelve patients had subclinical Cushing's syndrome, 41 had mild hormonal alterations, and 11 had normal adrenal function at baseline. All patients were investigated by morphological and functional evaluation 6 and 12 months after diagnosis, and then at 1-year intervals. RESULTS: During follow-up, a mass size increase >/=1 cm was observed in 13 patients, and 18 developed further subtle endocrine alterations. Cumulative risk of developing endocrine abnormalities was 17% at 1 year, 29% at 2 years, and 47% at 5 years. The risk was higher in the first 2 years of follow-up if the initial tumor diameter was >or=3 cm. Overall, cumulative risk of mass enlargement was 6% at 1 year, 14% at 2 years, and 29% at 5 years, and it was greater in patients with normal adrenal function than in those with subtle hormonal abnormalities (P<0.05). One female subject showed a mass enlargement after 6 months of follow-up and was eventually diagnosed with non-Hodgkin's lymphoma. CONCLUSIONS: Patients with an adrenal incidentaloma are at risk for tumor growth and development of hormonal alterations. The risk of adrenal malignancy, although not elevated, also indicates the need for long-term follow-up.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

[Risk factors of malignant skin melanoma in Italian population: review of results of a case-control study].

Cutaneous melanoma incidence rates are rapidly increasing worldwide, including in the Mediterranean countries. Sunlight exposure has been associated with melanoma, but the mechanisms of UV radiation-induced carcinogenesis is still largely unknown. In mammalian cells, UV radiation induces DNA damage that can be repaired mostly by the nucleotide excision repair system. We summarize here the results of a case-control study conducted at the Bufalini Hospital in Cesena, Italy to assess host and environmental risk factors for melanoma. We recruited 183 incident cutaneous melanoma cases and 179 controls selected predominantly among partners or close friends of the cases. Presence of dysplasticlatypical nevi (OR: 4.2; 95% CI: 2.4-7.4), low propensity to tan (OR: 2.4; 95% CI 1.1-5.0), light skin (OR: 4.1; 95% CI: 1.4-12.1), and light eye color (OR: 2.4; 95% CI: 1.1-5.2) were the strongest risk factors for melanoma in this population. A chart identifying melanoma risk associated with multiple combinations of these factors is presented. We used the host-cell reactivation assay on subjects' lymphocytes to measure individual DNA repair capacity (DRC) after UV-induced DNA damage. Subjects with low tanning ability and low DRC had a higher melanoma risk (OR: 8.6; 95% CI: 2.7-27.5) than those with higher tanning ability and high DRC. Subjects with dysplastic nevi and low DRC had a higher risk (OR: 6.7; 95% CI: 2.4-18.6) than those lacking dysplastic nevi and with high DRC. These results may help identify high-risk subjects in the Mediterranean populations who would the benefit from preventive measures.

Case-Control Studies↗