PCB Exposure and in Vivo CYP1A2 Activity among Native Americans

Abstract

Cytochrome P-450 1A2 (CYP1A2) is an enzyme involved in the metabolic activation of some carcinogens and is believed to be induced by xenobiotics. Very few studies, however, have investigated the association between environmental exposures and in vivo CYP1A2 activity in humans. To address this issue, a study was conducted of CYP1A2 activity among Native Americans exposed to polychlorinated biphenyls (PCBs) from the consumption of fish from the St. Lawrence River. At the Mohawk Nation at Akwesasne (in New York and in Ontario and Quebec, Canada), 103 adults were interviewed, and they donated blood for serum PCB analysis and underwent the caffeine breath test (CBT), a safe and noninvasive procedure that uses caffeine as a probe for CYP1A2 activity in vivo. The results supported the findings of other studies that CBT values are higher among smokers and men and lower among women who use oral contraceptives. Despite a relatively low average total PCB body burden in this population, the sum of serum levels for nine mono- or di-ortho-substituted PCB congeners showed positive associations with CBT values (p = 0.052 wet weight and p = 0.029 lipid adjusted), as did toxic equivalent quantities (TEQs; p = 0.091 for wet weight and 0.048 for lipid adjusted). Regarding individual congeners, serum levels of PCB-153, PCB-170, and PCB-180 were significantly correlated with CBT values. The results support the notion that CYP1A2 activity may be a marker of an early biological effect of exposure to PCBs in humans and that the CBT may be a useful tool to monitor such effects.

Effects of polychlorinated biphenyls on maternal odor conditioning in rat pups

“…Humans and other animals are continuously exposed to low levels of PCBs from soil, air and food sources [7,8]. In populations in which there are large amounts of fish consumption, PCBs can bioaccumulate and noticeably alter physical and motor development [9,10]. Studies on natural animal populations consistently find moderate-to-high levels of PCBs in many diverse animal groups [range in concentration from 3 to 500 ng/g; [11][12][13]] and it is principally unknown as to how this exposure influences development of psychological function.…”

The Ratio of Specific Polychlorinated Biphenyls as a Surrogate Biomarker of Cytochrome P4501A2 Activity—A Pharmaco-Metabonomic Study in Humans

“…The study population consisted of Mohawk men and women from the Mohawk Nation at Akwesasne, a Native American community along the St. Lawrence River in New York, Ontario, and Quebec (7). Briefly, of the 111 Mohawk women who became pregnant between April 1, 1992 and March 31, 1995 and of the 139 Mohawk men who were husbands or close relatives of the women, 172 agreed to undergo a CBT.…”

“…Sixty-eight PCB congeners were determined with gas chromatography with electron capture detection (7). The limits of detection were 0.02 ng/g wet weight for PCB153 and 0.01 ng/g for PCB118 and PCB105.…”

“…CYP1A2 activity was measured with a CBT (7). Labeled caffeine ( [3-13 C]methyl) was given in a dose of 3 mg/kg, up to a maximum of 200 mg. A 20-mL breath sample of expired air was collected immediately before and 30 and 60 min after ingestion of the labeled caffeine.…”

“…Ayotte et al (5) recently reported that the serum concentration ratio of PCB105/ PCB153 and that for PCB118/PCB153 significantly decreased with CYP1A2 activity, measured using a CBT among 20 subjects. They hypothesized that these ratios maybe useful surrogate biomarkers of CYP1A2 activity (6); in this article, we tested their hypothesis using data from a much larger study (7).…”