[Mechanism of the mutagenic/carcinogenic action of cigarette smoke at the pulmonary level: enzymatic induction, activation and detoxification].
Aryl hydrocarbon hydroxylase (AHH) and dimethylnitrosamine demethylase (DMND) activities in pulmonary and hepatic tissues of male Sprague-Dawley rats were assayed following pretreatment with known inducers (benzo(a)pyrene, 3-methylcholanthrene, Aroclor 1254, phenobarbital) and with mainstream (MS) and side-stream (SS) cigarette smoke condensate and their related fractions. Biochemical assays by spectrophotofluorimetry (AHH activity) and spectrophotometry (DMND activity) and by a biological assay (Ames test) were performed to detect AHH and DMND induction. Ames test proved to be much less sensitive than the spectrophotometric analysis for the AHH determination. Both main-stream and side-stream cigarette smoke condensates and some fractions, containing water-soluble bases, water-insoluble bases, and polycyclic aromatic hydrocarbons, were found to induce AHH activity in lung and liver, the lung being induced to the greatest extent. The highest levels of AHH inducibility were found for the SS-smoke condensate and related fractions. In particular, the insoluble-bases fraction gave the highest induction. On the contrary, pulmonary DMND activity was not affected by pretreatment with the same materials, while hepatic DMND response was only minimally induced by Aroclor and phenobarbital treatment. Twenty-two S12 preparations of surgical lung specimens obtained from smoker and non-smoker cancer patients were also assayed to detect aryl hydrocarbon hydroxylase (AHH), dimethylnitrosamine demethylase (DMND), and glutathione-S-transferase (GST) activities, in both normal and neoplastic lung tissue from the same patients. Pulmonary fractions were also tested for their ability to activate some precarcinogens into mutagenic metabolites in the Ames test. Statistically significant differences were found for AHH and DMND activities between normal and neoplastic tissue of smoker patients. In addition, higher AHH activity in the neoplastic tissue of the smoker group was observed compared with that found in the non-smoker group. No difference were found for GST activity. All the lung S12 preparations were able to metabolize water-soluble bases and water-insoluble bases, derived from main-stream cigarette smoke condensate, into mutagenic agents in the Salmonella test system. However, S12 preparations from smokers group neoplastic tissues were more effective.
Scassellati Sforzolini
G
G
Pasquini
R
R
Savino
A
A
Monarca
S
S
D000818:Animals; D001711:Biotransformation; D004790:Enzyme Induction; D006801:Humans; D008168:Lung / Q000201:enzymology*; D008175:Lung Neoplasms / Q000201:enzymology; D008297:Male; D009152:Mutagenicity Tests; D010947:Plants, Toxic; D051381:Rats; D011919:Rats, Inbred Strains; D012906:Smoke; D014026:Nicotiana
D012906:Smoke
Meccanismo dell'attivita' mutageno/cancerogena del fumo di sigaretta a livello polmonare: induzione enzimatica, attivazione e detossificazione.