Demetri M. Kokkinakis

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The effect of orotic acid (OA) on the carcinogenicity of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) in rats was evaluated. A group of 5 week old Sprague-Dawley male rats were placed on a synthetic 20% protein diet containing 1% OA. A second group was placed on a regular, OA-free diet of similar composition. Approximately 2 weeks later, animals from(More)
N-Nitrosobis(2-oxopropyl)amine (BOP) and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) alkylate DNA and other macromolecules in the liver, kidney, pancreas, and lungs when injected s.c. in the Syrian hamster. Two of the most abundant DNA adducts found were the N7-methylguanine and O6-methylguanine, which in the liver accounted for about 60% of total(More)
N-Nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) is a complete pancreatic carcinogen in female hamsters at a dose of 210 mg/kg given via an Alzet 2001 pump implanted s.c. Ultimate carcinogenic metabolites of HPOP target DNA to yield 7-and O6-methylguanines (7-mGua, O6-mGua) and 7- and O6-hydroxypropylguanines (7-HpGua, O6-HpGua). During continuous(More)
Rats and hamsters were administered a single dose of N-[1-14C]nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), and their urinary metabolites were examined at various time intervals. In both species, urinary excretion of radiolabeled metabolites reached a plateau at 6 h following injection. At this time, 35 and 28% of the total dose was found in the urine(More)
N.m.r. spectroscopy demonstrates that N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) exists as a mixture of four isomers, A, B, C and D, the equilibrium ratios of which are 57:8:16:19, respectively, at 25 degrees C. Two of these isomers, A and B, are rotomers of the open chain conformer, while the other two, C and D, are rotomers of the ring tautomer(More)
Liver preparations from Syrian golden hamsters catalyze the metabolism of the pancreatic carcinogen N-nitroso-2,6-dimethylmorpholine largely to N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP). This reaction is catalyzed by a mixed-function oxidase in the presence of reduced nicotinamide adenine dinucleotide phosphate and oxygen at a rate of 3.8(More)
The effect of continuous week-long administration of N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) by s.c. implanted osmotic pumps was examined in male and female Syrian hamsters given access to three isocaloric synthetic diets containing 10 (LP), 20 (MP) and 30% (HP) casein respectively. At a total dose of 210 mg/kg, toxicity of HPOP, expressed as(More)
Liver microsomes from male Syrian golden hamsters and Sprague Dawley rats metabolize the cis and trans isomers of N-nitroso-2,6-dimethylmorpholine (NNDM) to N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP) as the major product detectable by h.p.l.c. The rates of total metabolism are similar for both the cis and trans isomers; but the cis isomer of NNDM(More)
The effect of continuous week-long administration of the three pancreatic carcinogens N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), N-nitrosobis(2-hydroxypropyl)amine (BHP), and cis-N-nitroso-2,6-dimethylmorpholine (cis-NNDM), by a s.c. implanted osmotic pump, was examined in Syrian hamsters. HPOP at total doses of 220-250 mg/kg body weight induced(More)
/v-Nitroso-2,6-dimethylmorpholine (NNDM) is an indirect nitrosamine carcinogen which induces ductal adenocarcinoma of the pancreas in the Syrian golden hamster. NNDM is oxidized by normal male hamster pancreas postmitochondrial supernatants (S-9) in the presence of reduced nicotinamide adenine dinucleotide phosphate and oxygen to give three major identi(More)