Age dependent expression of cytochrome P-450b and metabolism of the potent carcinogen 2-nitrofluorene in the rat lung.
Northern and Western blot analyses, and analyses of microsomal metabolism of the carcinogen 2-nitrofluorene (NF) were conducted with the aim of studying age dependent cytochrome P-450b levels in the rat lung. The level of P-450b homologous mRNA and corresponding protein is very low in lungs from fetal and newborn rats. The levels then increase between 3 and 4 weeks of age, and reach adult levels at 6-8 weeks. No sex differences were detected with regard to lung P-450b mRNA levels or catalytical activities. Lung microsomal metabolism of NF increased in parallel with the accumulation of P-450b homologous mRNA and microsomal cytochrome P-450b protein concentration. Formation of the major metabolite, and potent mutagen, 9-hydroxy-2-nitrofluorene (9-OHNF) was significantly inhibited by addition of polyclonal anti-P-450b-IgG, and by addition of the inhibitor proadifen to incubations with lung microsomal protein. It is postulated that the observed, profound age-related differences in level and activity of lung cytochrome P-450b are likely to affect both availability and the ratio of metabolic detoxification and activation of chemical carcinogens deposited in the lung.
Törnquist
S
S
Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital, Sweden.
Sundin
M
M
Möller
L
L
Gustafsson
J A
JA
Toftgård
R
R
D015073:2-Acetylaminofluorene / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005449:Fluorenes / Q000378:metabolism*; D006900:Hydroxylation; D015151:Immunoblotting; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D005449:Fluorenes; D007527:Isoenzymes; D012333:RNA, Messenger; C019499:2-nitrofluorene; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene