Differential metabolism of benzo[alpha]pyrene in vitro by human placental tissues exposed to active maternal cigarette smoke.
OBJECTIVE
Generation of different metabolites and DNA-adduct(s) of metabolites of benzo[alpha]pyrene (B[alpha]P) in vitro by placental tissues (microsomes) of mothers who actively smoked cigarettes (tobacco) and those who did not smoke were analyzed to determine the variability in metabolism of the B[alpha]P substrate among individual placental samples.


METHODS
Overall B[alpha]P metabolism was assayed by alkaline aqueous extraction of metabolites, and reactive metabolites by DNA adducts of B[alpha]P-metabolites produced by salmon sperm DNA added to the incubation mixtures of the substrate and microsomes of exposed- and unexposed-placentas to maternal cigarette smoke. Array of B[alpha]P-metabolites produced by the same incubations were identified by high pressure liquid chromatography of the aqueous extracts.


RESULTS
Subsets of smoke-exposed placentas assessed by cluster analysis had augmented metabolic activity, others did not respond to smoke exposure. CYP1A1 expression in trophoblast cells analyzed by immunohistochemistry did not correlate with smoke exposure. The DNA-adducts generated was variable, regardless of verbally reported levels of maternal exposure. The amounts of different B[alpha]P-metabolites produced by individual samples matched for similar levels of exposure during pregnancy by self-reported smoking (1 pack/day) were also not comparable. Metabolism of B[alpha]P into different metabolites, and production of toxic DNA adducts from metabolites in vitro by human placenta were variable and unrelated to the extent of smoke exposure.


CONCLUSIONS
The metabolic characteristic of human placenta for xenobiotic exposure substrates is based on the expression and function of diverse enzymes, and such metabolism exhibited inter-individual variation for toxic metabolite production or detoxification of the substrates in response to maternal smoke exposure.
Sanyal
Mrinal K
MK
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University Medical School, New Haven, Connecticut, USA. sanyal@mmsj.att.net
Li
You Lan
YL
D001564:Benzo(a)pyrene / Q000378:metabolism*; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000032:analysis; D018736:DNA Adducts / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008861:Microsomes / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012907:Smoking / Q000378:metabolism*
D018736:DNA Adducts; D001564:Benzo(a)pyrene; D001579:Benzopyrene Hydroxylase; D019363:Cytochrome P-450 CYP1A1