Metabolic alterations produced by cigarette smoke in rat lung and liver, and their modulation by oral N-acetylcysteine.
Male Sprague-Dawley rats were exposed whole-body to the mainstream smoke produced by a commercial filter cigarette for 8 consecutive days, accounting for a cumulative exposure to the smoke of 75 cigarettes. Liver and lung S12 fractions were used in the Salmonella mutagenicity test in order to assess either the decrease of potency of a direct-acting mutagen (sodium dichromate) or the metabolic activation of promutagens, including cigarette smoke itself and its condensate, benzo[a]pyrene and its 7,8-diol, the aromatic amine 2-aminofluorene, and the heterocyclic amine 3-amino-1-methyl-5H-pyrido(4,3)indole. Moreover, individual biochemical parameters were measured in the liver and lung of the same rats and, in the case of cytochrome P-450-dependent monooxygenases, also in the heart of untreated or Aroclor-treated rats. The monitored biochemical parameters included aryl hydrocarbon (benzo[a]pyrene) hydroxylase and ethoxyresorufin deethylase in microsomal fractions, epoxide (benzo[a]pyrene-4,5-oxide) hydrolase in both microsomal and cytosolic fractions, glutathione (GSH) and GSH S-transferase in the cytosol. Exposure to cigarette smoke resulted in a number of significant metabolic changes, as compared to sham-exposed rats. The most pronounced alterations consisted in a 2.6-fold induction of aryl hydrocarbon hydroxylase in the lung and 8-fold induction of ethoxyresorufin deethylase in the liver, and in a marked stimulation of the liver metabolic activation of all promutagens. The last effect was inhibited by the oral administration of the chemopreventive agent N-acetylcysteine. On the whole, there was a poor correlation between the monitored biochemical and mutagenicity endpoints.(ABSTRACT TRUNCATED AT 250 WORDS)
Bagnasco
M
M
Institute of Hygiene and Preventive Medicine, University of Genoa, Italy.
Bennicelli
C
C
Camoirano
A
A
Balansky
R M
RM
De Flora
S
S
D000111:Acetylcysteine / Q000008:administration & dosage*; D000284:Administration, Oral; D000818:Animals; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000378:metabolism; D010947:Plants, Toxic; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000235:genetics; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
D009153:Mutagens; D012906:Smoke; D000111:Acetylcysteine