RT Journal Article
SR Electronic
T1 Effect of tobacco smoke condensate on the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by adult and fetal hamster microsomes.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 318
OP 324
VO 21
IS 2
A1 R Jorquera
A1 A Castonguay
A1 H M Schuller
YR 1993
UL http://dmd.aspetjournals.org/content/21/2/318.abstract
AB The tobacco-specific N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen in Syrian golden hamsters exposed pre- or postnatally to NNK. NNK requires metabolic activation, mainly by the cytochrome P-450 monooxygenase system, to exert its carcinogenic activity. Along with carcinogens, tobacco smoke contains other biologically active substances such as enzyme inducers and inhibitors. In this study, we have investigated the effects of tobacco smoke condensate (TSC) on microsomal metabolism of NNK in hamsters. TSC was instilled intratracheally to non-pregnant and pregnant hamsters on days 12, 13, and 14 of gestation. Following euthanasia on day 15 of gestation, liver and lung microsomes from adult and fetal hamsters were prepared, and the metabolism of NNK was analyzed by HPLC. Although TSC tended to increase the formation of some alpha-carbon hydroxylation metabolites with liver microsomes from adult hamsters, none of the metabolic pathways of NNK showed a statistically significant increase or decrease caused by TSC exposure. Similarly, no significant alterations of NNK metabolism were observed with lung microsomes from TSC-treated adult hamsters, as well as with liver or lung microsomes from fetal hamsters exposed in utero to TSC. As shown by Western blotting analyses, the protein levels of the P-450 enzymes most likely involved in NNK metabolism (i.e. P-450IIB1 and P-450IIE1) remained almost unchanged in liver or lung microsomes from TSC-exposed hamsters. Interestingly, the P-450IIB1 protein content was increased in lung microsomes from TSC-treated pregnant hamsters, an effect likely related to the altered hormonal status of these animals.(ABSTRACT TRUNCATED AT 250 WORDS)