TY - JOUR
T1 - Metabolism of the hamster pancreatic carcinogen methyl-2- oxopropylnitrosamine by hamster liver and pancreas
AU - Chen, Sheng C.
AU - Wang, Xiaojie
AU - Zhou, Lin
AU - Kolar, Carol
AU - Lawson, Terence A.
AU - Mirvish, Sidney S.
N1 - Funding Information:
This research was supported by a grant from the Nebraska Department of Health and by core grant P30-CA-36727 from the National Cancer Institute.
PY - 2000
Y1 - 2000
N2 - Background. The mechanism whereby methyl-2-oxopropylnitrosamine (MOP) is activated remains unknown. To begin investigating this mechanism, we followed MOP disappearance during its incubation with liver and pancreatic slices and homogenates from Syrian hamsters and rats. Methods. After the incubations, disappearance of 100 μM MOP and appearance of a metabolite was followed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results. Disappearance rates were 1.2 nmol/mg protein/h for hamster liver slices; zero for hamster pancreatic slices, ducts and acini; zero for rat liver and pancreatic slices; and 11.8, 12.8, 1.3, and 2.3 nmol MOP/mg/h for hamster liver homogenate and cytosol, and hamster pancreas homogenate and microsomes, respectively. The principal MOP metabolite was identified as methyl-2-hydroxypropylnitrosamine (MHP) by its HPLC behavior and its 1H-NMR and mass spectra. MHP yields were generally similar to MOP consumption, but were zero for hamster pancreatic homogenate despite its ability to metabolize MOP. Conclusion. MOP is a pancreatic carcinogen in hamsters but not in rats. In metabolic studies, hamster liver slices and homogenate (especially the cytosol) produced MHP from MOP. This is probably an inactivation reaction. Hamster pancreas homogenate (especially the microsome fraction), but not rat pancreas homogenate, metabolized MOP without forming MHP, indicating another route of metabolism, perhaps activation to give the proximal carcinogen.
AB - Background. The mechanism whereby methyl-2-oxopropylnitrosamine (MOP) is activated remains unknown. To begin investigating this mechanism, we followed MOP disappearance during its incubation with liver and pancreatic slices and homogenates from Syrian hamsters and rats. Methods. After the incubations, disappearance of 100 μM MOP and appearance of a metabolite was followed by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results. Disappearance rates were 1.2 nmol/mg protein/h for hamster liver slices; zero for hamster pancreatic slices, ducts and acini; zero for rat liver and pancreatic slices; and 11.8, 12.8, 1.3, and 2.3 nmol MOP/mg/h for hamster liver homogenate and cytosol, and hamster pancreas homogenate and microsomes, respectively. The principal MOP metabolite was identified as methyl-2-hydroxypropylnitrosamine (MHP) by its HPLC behavior and its 1H-NMR and mass spectra. MHP yields were generally similar to MOP consumption, but were zero for hamster pancreatic homogenate despite its ability to metabolize MOP. Conclusion. MOP is a pancreatic carcinogen in hamsters but not in rats. In metabolic studies, hamster liver slices and homogenate (especially the cytosol) produced MHP from MOP. This is probably an inactivation reaction. Hamster pancreas homogenate (especially the microsome fraction), but not rat pancreas homogenate, metabolized MOP without forming MHP, indicating another route of metabolism, perhaps activation to give the proximal carcinogen.
KW - Hamster pancreas
KW - Ketone reduction
KW - Metal-working fluids
KW - Methyl-2-hydroxypropylnitrosamine
KW - Methyl-2-oxopropylnitrosamine
KW - Pancreatic carcinogenesis
UR - http://www.scopus.com/inward/record.url?scp=0034080195&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034080195&partnerID=8YFLogxK
U2 - 10.1385/ijgc:27:2:105
DO - 10.1385/ijgc:27:2:105
M3 - Article
C2 - 10862509
AN - SCOPUS:0034080195
SN - 0169-4197
VL - 27
SP - 105
EP - 112
JO - International Journal of Pancreatology
JF - International Journal of Pancreatology
IS - 2
ER -