Lawrence Wallcave

Bio: Lawrence Wallcave is an academic researcher from University of Nebraska Medical Center. The author has contributed to research in topics: Hamster & Morpholine. The author has an hindex of 15, co-authored 24 publications receiving 1308 citations.

Ascorbate-Nitrite Reaction: Possible Means of Blocking the Formation of Carcinogenic N-Nitroso Compounds

Abstract: The formation of carcinogenic N-nitroso compounds by the chemical reaction between nitrous acid and oxytetracycline, morpholine, piperazine, N-methylaniline, methylurea, and (in some experiments) dimethylamine was blocked by ascorbic acid. The extent of blocking depended on the compound nitrosated and on the experimental conditions. Urea and ammonium sulfamate were less effective as blocking agents. The possibility of in vivo formation of carcinogenic N-nitroso compounds from drugs could be lessened by the combination of such drugs with the ascorbic acid.

Current knowledge of pancreatic carcinogenesis in the hamster and its relevance to the human disease

Abstract: Syrian hamsters present a unique species for induction of pancreatic tumors that in many aspects resemble human pancreatic cancer. The specific response of Syrian hamsters, in contrast to may other rodents, for development of pancreatic ductal (ductular) tumors is not yet known. All pancreatic carcinogens thus far tested show certain common features. They are all nitrosamines that possess or can be metabolized to compounds with 2-oxopropyl- or 2-hydroxypropyl substituents. All but one, N-nitroso-methyl(2-oxopropyl)amine, occur or metabolize to nitrosamines with the ability to cyclize and form structures resembling glucose. Hence it is suggested that this cyclic structure may be responsible for the pancreatic carcinogenicity of these nitrosamines, as has been proposed for the pancreatotropic effect of streptozotocin. It is also of further interest that one pancreatic ductal (ductular) carcinogen, N-nitroso-2-methoxy-2,6-dimethylmorpholine, which possesses a totally cyclic structure, acts, like streptozotocin, as beta-cell cytotoxic and diabetogenic when given in a high single dose. Modification of pancreatic tumor induction has been demonstrated by specific procedures. A high fat diet significantly increases both the incidence and number of induced cancers. Methods for early diagnosis and therapy are being developed and their significance and applicabilities for clinical use will be of major importance. Compared with the other most common types of human cancer, pancreatic cancer has extraordinary characteristics, which make the disease one of the most mysterious of maladies. Consequently, pancreatic cancer represents a serious international problem and requires urgent resolution, especially with regard to its etiology, early diagnosis, prevention, and therapy.

Induction of Mouse Lung Adenomas by Amines or Ureas Plus Nitrite and by N-Nitroso Compounds: Effect of Ascorbate, Gallic Acid, Thiocyanate, and Caffeine

Abstract: Lung adenomas were induced in strain A mice by chronic treatment with N-nitroso compounds (given in drinking water) and with amines or ureas in food plus NaNO2 in drinking water. We studied the effects of varying the concentrations of three N-nitroso compounds and NaNO2 concentration in the morpholine plus NaNO2 and methylurea plus NaNO2 systems. Sodium ascorbate (NaASC) at the highest level tested (11.5 or 23 g/kg food) gave 89-98% inhibition of adenoma induction by the NaNO2 plus piperazine, morpholine, and methylurea systems. In 7 groups, NaASC produced increases of 15-59% in adenoma induction by nitrosomorpholine (NM) and mononitrosopiperazine (MNP), possibly because the mice consumed more of the nitrosamine solution. Adenoma induction by morpholine plus NaNO2 was strongly inhibited by gallic acid, moderately inhibited by caffeine, and unaffected by thiocyanate (all added to the food). Gallic acid inhibited or had no effect on the action of NM and MNP. We discussed the proposal that NaASC (or perhaps gallic acid) be administered with readily nitrosatable drugs.

Metabolism of the Pancreatic Carcinogens N-Nitroso-bis(2-oxopropyl)amine and N-Nitroso-bis(2-hydroxypropyl)amine in the Syrian Hamster

Abstract: Metabolisms of the potent pancreatic carcinogens N-nitroso-bis(2-oxopropyl)amine (BOP) and N-nitroso-bis(2-hydroxypropyl)amine (BHP) were studied in male Syrian hamsters. BHP and a new metabolite, N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), were detected in the urine of hamsters administered BOP and BHP. The rates of HPOP formation from BOP and BHP were determined by the measurement of blood and urine levels at various times after each compound was administered: HPOP was formed readily from BOP, but slowly from BHP. This may explain the different organotropic spectra and carcinogenic potencies of BOP and BHP.

The Merck Index

Abstract: The Merck Index of Chemicals and Drugs An Encyclopedia for the Chemist, Pharmacist, Physician and Allied Professions Sixth edition Pp xiv + 1167 (Rahway, NJ: Merck and Company, Inc, 1952) 750 dollars; thumb-indexed, 8 dollars

Role of Life-style and Dietary Habits in Risk of Cancer among Seventh-Day Adventists

Abstract: The Seventh-Day Adventist population abstains from smoking and drinking; about 50% follow a lacto-ovo-vegetarian diet; and most avoid the use of coffee, tea, hot condiments, and spices. Existing data on cancer mortality in Seventh-Day Adventists clearly document mortality rates that are 50 to 70% of general population rates for most cancer sites that are unrelated to smoking and drinking. Several approaches to determining whether this reduced risk is due to the unique Seventh-Day Adventist life-style or selective factors related to who choses to become and remain a Seventh-Day Adventist are described. A comparison of the mortality experience of Seventh-Day Adventist and non-Seventh-Day Adventist physicians shows equal cancer mortality, which is consistent with the hypothesis that the apparent reduced risk of cancer death in all Adventists may be due to selective factors. However, the results of a small case-control study of colon and breast cancer among Adventists show statistically significant relative risks for colon cancer of 2.8 for past use of meat. For current food use, the significant relative risks are 2.3 for beef, 2.7 for lamb, and 2.1 for a combined group og highly saturated fat foods. This strongly suggests that the lacto-ovo-vegetarian diet may protect against colon cancer. However, the evidence linking diet to breast cancer is less clear. Because of the marked variability in dietary habits within the Seventh-Day Adventist population, they will be a productive group for further study of diet and cancer.