Unilateral transplantation of porcine embryonic VM cells into PD patients was well tolerated with no evidence of transmission of porcine endogenous retrovirus. Changes in standardized clinical PD rating measures were variable, similar to the results of the first trials of unilateral human embryonic allografts that transplanted small amounts of tissue.

The observation that fetal neurons are able to survive and function when transplanted into the adult brain fostered the development of cellular therapy as a promising approach to achieve neuronal replacement for treatment of diseases of the adult central nervous system. This approach has been demonstrated to be efficacious in patients with Parkinson's disease after transplantation of human fetal neurons. The use of human fetal tissue is limited by ethical, infectious, regulatory, and practical concerns. Other mammalian fetal neural tissue could serve as an alternative cell source. Pigs are a reasonable source of fetal neuronal tissue because of their brain size, large litters, and the extensive experience in rearing them in captivity under controlled conditions. In Phase I studies porcine fetal neural cells grafted unilaterally into Parkinson's disease (PD) and Huntington's disease (HD) patients are being evaluated for safety and efficacy. Clinical improvement of 19% has been observed in the Unified Parkinson's Disease Rating Scale "off" state scores in 10 PD patients assessed 12 months after unilateral striatal transplantation of 12 million fetal porcine ventral mesencephalic (VM) cells. Several patients have improved more than 30%. In a single autopsied PD patient some porcine fetal VM cells were observed to survive 7 months after transplantation. Twelve HD patients have shown a favorable safety profile and no change in total functional capacity score 1 year after unilateral striatal placement of up to 24 million fetal porcine striatal cells. Xenotransplantation of fetal porcine neurons is a promising approach to delivery of healthy neurons to the CNS. The major challenges to the successful use of xenogeneic fetal neuronal cells in neurodegenerative diseases appear to be minimizing immune-mediated rejection, management of the risk of xenotic (cross-species) infections, and the accurate assessment of clinical outcome of diseases that are slowly progressive.

Our results demonstrate by both examination of transplant patient blood samples and in vitro studies that there is no evidence for transmission of PERV from porcine fetal neural cells to human cells.

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N'-Nitrosonornicotine (NNN) and N'-nitrosoanabasine (NAB) were synthesized and administered in drinking water to male Fischer rats for 30 weeks (total dose, 630 mg). 1,4-Dinitrosopiperazine (DNPI) served as the positive control. By 11 months, all surviving rats given NNN developed esophageal tumors (12/20); 1 had a pharyngeal tumor and 3 had invasive carcinomas originating in the nasal cavity. During the same time, only 1 of 20 rats given NAB developed esophageal tumors. Compared to the strong esophageal carcinogen DNPI, NNN was a moderately active and NAB a weak carcinogen. NNN (0.3-90 parts per million) in chewing tobacco was related to the observation that cancer of the oral cavity and esophagus in man was correlated with the chewing of tobacco.

The formation of nitrite from nitrate was studied in potatoes incubated at room temperature. After 24 hours of incubation at 25 degrees, 112 ppm and 373 ppm of nitrite formed in homogenized cooked potatoes containing 284 ppm and 584 ppm of nitrate, respectively. In homogenized fresh potatoes incubated at 21 degrees and containing 284 ppm of nitrate, 103 ppm of nitrate formed within 24 hours. During the period of nitrite formation, nitrate levels decreased sharply, indicating that reduction of nitrate to nitrite occurred. Incubation at 2 degrees completely prevented nitrite formation in all cases. The formation of methylnitrosourea from added methylurea and nitrite was observed in potato incubated under simulated gastric conditions (37 degrees, pH 1.5). An ascorbate-nitrite mole ratio of 4 gave a 93% inhibition of methylnitrosourea formation. Ascorbate reacted directly with nitrite in potato incubated under identical conditions, yielding a 43% decrease in nitrite concentration. Ascorbate did not react with methylurea or the product, methylnitrosourea.

Before exerting a carcinogenic o r mutagenic effect, many carcinogens must undergo metabolic activation. Liver S-9 preparations from rats treated with Aroclor 1 2 5 4 (AC) have been widely used to extend the ability of the Salmonella mutagenicity assay t o detect such nondirect-acting agents. We compared the mutagen-activating capabilities of liver S-9 preparations f r o m both Syrian golden hamsters and Sprague-Dawley rats. T h e comparison was made between S-9 fractions from untreated, and phenobarbital (PB)-and AC-treated animals of both sexes. Also compared was the effect of varying the amount of S-9 protein. T h e preparations from hamster liver were consistently more effective than preparations from rat liver for the activation of 2-acetylaminofluorene (AAF), 2-aminoanthracene (AA) (except for ACinduced preparations), 3-methylcholanthrene (MCA), and diethylnitrosamine (DEN) t o their mutagenic forms. Induced preparations from rats were more active than those from hamsters when using benzo(a)pyrene (BP), while with uninduced preparations, the opposite was true.There was also a relationship between the a m o u n t of S-9 protein and the number of revertant colonies obtained. With the aromatic aniines ( A A F and AA), a partial inhibition of mutagenicity occurred at the highest protein concentrations tested. With BP, a n inverse relationship was observed between protein concentration and the number of revertants occurring in the presence of the preparation from PB-and AC-induced male and female rats.T h e relative order of activities of aryl hydrocarbon hydroxylase (AHH) and BP-4,Sepoxide hydrase (EH) in the preparations was AC-induced > PBllie abbreviations used are: AC.

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