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R Saracci

Publications and source records attributed to R Saracci.

63 records · Page 4Linked to original sources

Carcinogen metabolism and DNA adducts in human lung tissues as affected by tobacco smoking or metabolic phenotype: a case-control study on lung cancer patients.

Individual variations in activity of pulmonary enzymes that metabolize tobacco-derived carcinogens may affect an individual's cancer risk from cigarette smoking. To investigate whether some of these enzymes (e.g., cytochrome P450IA-related) can serve as markers for carcinogen-induced DNA damage accumulating in the lungs of smokers, non-tumorous lung tissue specimens were taken during surgery from middle-aged men with either lung cancer (n = 54) or non-neoplastic lung disease (n = 20). Phase I (AHH, ECDE) and phase II (EH, UDPGT, GST) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were analyzed for DNA adducts, using 32P-postlabeling. Data analysis of subsets or the whole group of patients yielded the following results. (1) Phase I and II drug-metabolizing enzyme (AHH, EH, UDPGT, GST) activities in histologically normal surgical specimens of lung parenchyma were correlated with the respective enzyme activities in bronchial tissues of the same subject. (2) In lung parenchyma, enzyme (AHH, ECDE, EH, UDPGT) activities were significantly and positively related to each other, implying a similar regulatory control of their expression. (3) Mean activities of pulmonary enzymes (AHH, ECDE) were significantly (2- and 7-fold, respectively) higher in lung cancer patients who had smoked within 30 days before surgery (except GST, which was depressed) than in cancer-free subjects with a similar smoking history. (4) In the cancer patients, the time required for AHH, EH and UDPGT activities to return to the level found in non-smoking subjects was several weeks. (5) Bronchial tree and peripheral lung parenchyma preparations exhibited a poor efficiency in activating promutagens to bacterial mutagens in Salmonella. However, they decreased the mutagenicity of several direct-acting mutagens, an effect which was more pronounced in tissue from recent smokers. GSH concentration and GST activity were positively correlated with mutagen inactivation in the same sample. (6) In recent smokers, AHH activity in lung parenchyma was positively correlated with the level of tobacco smoke-derived DNA adducts. (7) Pulmonary AHH and EH activity had prognostic value in tobacco-related lung cancer patients. (8) An enhanced level of pro-oxidant state in the lungs was associated with recent cigarette smoking. Malondialdehyde level in lung parenchyma was associated with the degree of small airway obstruction, suggesting a common free radical-mediated pathway for both lung cancer induction and small airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Epidemiologic studies on carcinogenic risk and occupational activities in tanning, leather and shoe industries].

A review is made of the epidemiological studies of occupational cancer risks among tannery, leather and shoe industry workers. The risk of nasal cancer associated with exposure to leather dust, which had already been stressed at the beginning of the 1970's, was confirmed in recent studies. However, a decreasing trend of RR was observed among shoe industry workers. The excess of leukemia among shoe workers, which was mainly based on the description of numerous cases of acute myeloblastic leukemia, has also been confirmed by two cohort studies carried out in Italy and the U.K. In addition to the evident increase in these two diseases, there are indications of an excess of cancer of other sites among leather and shoe workers, particularly bladder cancer, both among workers assigned to leather finishing operations and in leather goods and shoe production workers. Another interesting result is the excess of lung cancer among tannery workers. This evidence is unanimous in the studies carried out in Italy but is not supported by the majority of studies performed in other countries. For this reason, we consider it extremely important to carry out a multicentric study in Italy, with particular attention to the definition of occupational exposures to carcinogens. There are also other isolated reports of excesses of other cancers in the shoe and leather industries but in our opinion they are of dubious interpretation.

Dust