Reference

Induction of rat pancreatic B-cell tumors by the combined administration of streptozotocin or alloxan and poly(adenosine diphosphate ribose) synthetase inhibitors

Induction of rat pancreatic B-cell tumors by the combined administration of streptozotocin or alloxan and poly(adenosine diphosphate ribose) synthetase inhibitors. Yamagami, Takashi; Miwa, Atsuo; Takasawa, Shin; Yamamoto, Hiroshi; Okamoto, Hiroshi (Sch. Med., Toyama Med. Pharm. Univ., Toyama 930-01, Japan). Cancer Res., 45(4), 1845-9 (English) 1985. CODEN: CNREA8. ISSN: 0008-5472. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 4, 14 Streptozotocin [18883-66-4] and alloxan [50-71-5] were administered to Wistar rats in combination with poly(ADP ribose)synthetase [9055-67-8] inhibitors. Ten to 16 mo after the injection of streptozotocin (50 mg/kg i.v.) and 3-aminobenzamide [3544-24-9] (345 mg/kg i.v.), streptozotocin (50 mg/kg) and nicotinamide [98-92-0] (350 mg/kg i.p.), streptozotocin (50 mg/kg) and picolinamide [1452-77-3] (250 mg/kg i.p.), alloxan (40 mg/kg i.v.) and nicotinamide (350 mg/kg), and alloxan (40 mg/kg) and picolinamide (250 mg/kg), pancreatic islet cell tumors developed in 100, 98, 60, 26, 22, and 20% of surviving rats, resp. However, after the single injection of streptozotocin and alloxan, islet cell tumors developed in 42 and 11% of surviving rats, resp. The tumors were rich in B-granules on electron micrographs and contained as large amts. of proinsulin mRNA as normal pancreatic islets. The results indicate that poly(ADP ribose)synthetase inhibitors enhance the tumorigenic effect of streptozotocin and alloxan on islet B-cells.

Nature of N-nitrosodimethylamine demethylase in hepatic microsomes of rats

Nature of N-nitrosodimethylamine demethylase in hepatic microsomes of rats. Kawanishi, T.; Ohno, Y.; Takahashi, A.; Takanaka, A.; Kasuya, Y.; Omori, Y. (Biol. Saf. Res. Cent., Natl. Inst. Hyg. Sci., Tokyo 158, Japan). Arch. Toxicol., 56(1), 7-11 (English) 1984. CODEN: ARTODN. ISSN: 0340-5761. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) The nature of enzymes involved in demethylation of N-nitrosodimethylamine (NDMA) [62-75-9] was investigated in hepatic microsomes of rats. Kinetic anal. suggested a qual. change in NDMA demethylase (I) [69772-95-8] induced by phenobarbital (PB) [50-06-6] and 3-methylcholanthrene (MC) [56-49-5] pretreatment. The inhibition of I by a-naphthoflavone [604-59-1] in MC-treated microsomes suggested that cytochrome P 450 [9035-51-2] species induced by MC were active in demethylating NDMA. The enhancement of I activity by metyrapone [54-36-4] in PB-treated microsomes was greater than in nontreated ones, and was not obsd. in MC-treated ones. Pyrazole [288-13-1], tranylcypromine [155-09-9], and aminoacetonitrile [540-61-4], which are selective inhibitors of NDMA demethylation, interacted with cytochrome P 450 species to produce type-II spectra, and typical type-II compds. (aniline [62-53-3], imidazole [288-32-4], and nicotinamide [98-92-0]) were inhibitors of the NDMA demethylation. Tranylcypromine [155-09-9] irreversibly inhibited microsomal monoamine oxidase [9001-66-5] but not NDMA demethylase. Semicarbazide [57-56-7] had no effect on demethylation. Thus, NDMA demethylation depended only on cytochrome P 450-dependent monooxygenases.