Cholecystokinin inhibits DNA alkylation induced by N-nitrosobis (2-oxopropyl)amine (BOP) in hamster pancreas.

Cholecystokinin (CCK) inhibits pancreatic cancer but not hepatic tumor induction by N-nitrosobis (2-oxopropyl) amine (BOP) in hamsters when administered with or shortly before BOP. In this study, we evaluated the capability of sulfated CCK-8 to inhibit DNA alkylation in the hamster pancreas. We examined the pattern of O6-methylguanine (G6-Me) and N7-methylguanine (G7-Me) in pancreatic ductal, acinar and liver tissues from Syrian hamsters treated with a single dose of BOP (20 mg/kg s.c.) and with five s.c. injections of CCK-8 (200 pM/kg, 30 min apart). The first CCK injection was given either 90 min before, or together, or 3 h after POP administration. The amount of G6-Me in liver DNA did not differ significantly. We observed a decrease of G7-Me in the liver of the group treated with CCK together with POP as compared to POP alone (P less than 0.005). Lower amounts of G6-Me were found in ductal preparations (P less than 0.01) of the animals treated with CCK before POP as compared to POP alone. CCK also modified the pattern of alkylation in the acinar tissue, but without a clear relationship with the timing of administration. The results suggest that the inhibitory effect of CCK-8 on pancreatic carcinogenicity of BOP could be related to its capability to modify DNA alkylation by yet unknown mechanisms.     

Enhanced levels of annexins in pancreatic carcinoma cells of Syrian hamsters and their intrapancreatic allografts.

Annexins are a family of calcium- and phospholipid-binding proteins related by amino acid sequence homology. Annexins I and II are substrates for protein tyrosine kinases. Recent investigations have revealed a possible involvement of annexins I and II in mitogenic signal transduction and cell proliferation. To investigate further the involvement of annexins in cell proliferation, we measured the levels of annexins I and II and the enzyme 3-phosphoglycerate kinase (PGK) (annexin II and PGK are components of the primer recognition protein complex) in normal Syrian hamster pancreas, three hamster pancreatic ductal carcinoma cell lines, and allografts of the three cell lines into hamster pancreas. All three carcinoma cell lines had 5-8-fold higher levels of annexin II compared to normal pancreas. An inverse relationship was seen between level of annexin II and the doubling time of the cell culture. In intrapancreatic allografts, annexin II levels were 3-6-fold higher than in normal pancreas. Annexin I levels were 2-3-fold higher in the allografts. Significant increases (5-6-fold) in specific activity of PGK were seen in all allografts examined. However, the level of PGK, as measured by immunoblotting, was not significantly altered. Immunohistochemical staining revealed heterogeneity in the reactivity of the antiannexin and anti-PGK antibodies with tumor cells. Strikingly, the reactivity and staining intensity were greater in the proliferating regions of the primary tumors and in the metastatic foci. Mitotic cells were either unstained or very weakly stained. We conclude from these findings that annexin II and PGK, as primer recognition proteins, may have a role in cell proliferation.     

Feeding and locomotion responses to centrally injected nociceptin/orphanin FQ in chicks

Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid receptor-like receptor or nociceptin receptor (NOP), has been shown to induce feeding, locomotion, anti-stress and anxiolytic effects in rodents after central nervous system injection. In this study, the effect of intracerebroventricular (icv) injection of N/OFQ on feeding and locomotion behavior was evaluated in male broiler-type chickens. The icv injection of N/OFQ caused a moderate but significant increase in feed intake similar to the classical opioid peptides in rats. It also increased feed pecking frequency and feeding time 1 h after injection. Stepping, wing flapping and preening were not affected by N/OFQ. These results suggest that N/OFQ can act within the central nervous system of chickens to increase feed intake.     

Modification of pancreatic carcinogenesis in the hamster model. 6. The effect of ductal ligation and excision

The effect of ligation and excision of the pancreatic duct in pancreatic carcinogenesis was examined in the hamster model. Animals were treated with a single dose (20 mg/kg body weight) of N-nitrosobis(2-oxopropyl)amine (BOP) either immediately (Group 1) or on Days 1 (Group 2), 3 (Group 3) or 7 (Group 4) after ligation and excision of the duct of the splenic lobe. Group 5 received BOP shortly after laparoscopy, and Group 6 consisted of BOP-treated controls. All hamsters were killed 46 weeks after BOP treatment. The results showed that despite advanced atrophy of the splenic lobe distal to the excised duct in Groups 1-4, some hamsters in Groups 2, 3, and 4 showed hyperplasia, dysplasia, and increased mitotic activities of ductal and ductular cells. However, carcinomas in the duct-excised atrophic lobe were found only in Groups 1-3. These data indicate that BOP carcinogenesis is mediated through blood circulation, and that cancer development is not inhibited in the duct-excised lobe for up to 3 days after surgery. However, in the entire pancreas, a significant reduction in tumor incidence was seen when the carcinogen was given immediately, or to a lesser extent, 1 day after surgery, regardless of whether or not excision was made. On the contrary, BOP, when given 3 and 7 days after duct excision, enhanced tumor development in the nonexcised (intact) pancreas, compared with other test groups and with BOP controls. Both inhibition and enhancement seemed due to a proportional decrease and increase, respectively, of BOP-responsive cells throughout the intact pancreas.     

Enhanced pancreatic and skin tumorigenesis in cabbage-fed hamsters and mice

Studies were conduded to evaluate the ability of dietary driedcabbage supplements to inhibit pancreatic carcinogenesis inhamsters and skin tumorigenesis in mice. Pancreatic cancer wasinduced by treatment with 40 mg/kg body wt N-nitrosobis-(2oxopropyl)amine(BOP). Cabbage was fed from before carcinogen treatment in lowfat diet and, beginning 1 week after BOP treatment, cabbagewas given in low fat and high fat diets in comparison with therespective non-cabbage containing diets. Dried cabbage was incorporatedat 9 and 11% levels into the low and high fat diets. Feedingcabbage in the high fat diet elevated the yield of BOP-inducedpancreatic ductular cardnoma (1.6 carcinomas/effedive animal)in comparison with that observed in hamsters fed cabbage ina low fat diet or in those given a high fat diet without cabbage, 0.6–0.8 carcinomaa/effedive animal (P 0.05). Furthermore,the incidence of BOP-induced gall bladder adenocadnomm was elevatedin cabbage-fed hamsters irrespedve of dietary fat intake. Effetsof dietary fat and cabbage on food consumption, body weight,and serum T₃ and T₄ values are described. Skin tumorigenesiswas induced in SENCAR mice by 10 nmd 7,12 dlmethylbenz[a]anthracene(DMBA) and promoted beginning 1 week later with twice weeklyapplications of 2 µg 12-O-tetradecanoyl-13-phorbol acetate(TPA). Dried cabbage was incorporated into AIN semi-purifieddiets from before DMBA treatment and throughout TPA treatment.Skin papilloma yield was elevated in DMBA-initiated TPA-promotedmice that were fed diets containing 10% cabbage. Mice fed cabbagedeveloped an average of 8.45 papillomas per mouse following22 weeks of promotion while mice given control diet developed7.25 papillomas per mouse (P < 0.001). Cabbage feeding didnot influence survival, food consumption or body weight of themice. These results suggest the need for further research onthe use of cabbage as a chemopreventive measure.     

Endoscopic stapedotomy: Merits and demerits

A one-year-old baby girl with one-month history of recurrent pus fluid exuding from her left preauricular sinus orifice, who failed multiple courses of surgical drainage of the abscess and persistent debridement for the wound, presented with MRSA infection. The patient was treated with linezolid for three days. Her pain and paresthesia resolved, and C-reactive protein decreased to normal.