Carcinogenic arylamines are acetylated by the hepatic N-acetyltransferase. This enzyme is polymorphic in humans and in some epidemiological studies, the slow-acetylator phenotype has been associated with higher risk of bladder cancer and lower risk of colorectal cancer. The presence of two germline copies of any of several mutant alleles of the NAT2 gene produces a slow-acetylation phenotype. We used a PCR-RFLP technique to identify three known slow-acetylator alleles (M1, M2 and M3). Comparison of results from PCR-RFLP genotyping with caffeine metabolism phenotyping in 42 individuals suggested that an additional slow-acetylator allele was present in our sampled population. We sequenced the NAT2 gene for several discordant slow-acetylator individuals and found a G > A base-change in codon 64 that caused a Arg > Glu amino acid substitution. This sequence change, termed the 'M4' allele, was found in all of the discordant individuals in our population and apparently causes a slow-acetylation phenotype. In addition, we have determined that NAT2 allele frequencies in 372 Caucasian-Americans (WT = 0.25, M1 = 0.45, M2 = 0.28, M3 = 0.02, and M4 = 0.00) and in 128 African-Americans (WT = 0.36, M1 = 0.30, M2 = 0.22, M3 = 0.02 and M4 = 0.09) are significantly different (P < 0.0001). The M4 allele was not found in 372 unrelated Caucasians and appears to be of African origin.

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A continuous lymphoblastoid cell line was established from a JMV tumor transplant related to Marek's disease (MD). It is designated RPL1 (JMV) lymphoblastoid cell line. This cell line contains DNA sequences complementary to MD virus DNA and has an antigen similar to MD-tumor-associated surface antigen (MATSA). However, it lacks any MD virus (MDV) rescuable in vivo or in vitro. The cell line has surface antigens typical of chicken thymus cells (T cells) and histocompatability antigens different from those of the host chicken.

Many pediatric and adolescent cancer patients are treated with carcinogenic chemotherapeutic agents and radiation therapy to achieve permanent control of their malignancy. These modalities may induce a new cancer in the successfully treated patient. To identify disease and treatment factors which increased the risk of occurrence of a second malignant tumor following modern treatment for cancer during childhood or adolescence, we reviewed the courses of 1,406 previously untreated patients who were less than 20 years of age at diagnosis and were treated at Roswell Park Cancer Institute between January 1, 1960 and December 31, 1989. Eighteen patients developed a second malignant tumor, including two meningiomas, 2.65-25.65 years after diagnosis of the first cancer. The actuarial risk of a second malignant tumor was 5.6% at 25 years after diagnosis. Using Cox proportional hazards modelling, we identified prior therapy with BCNU (P = 0.0055) and doxorubicin (P = 0.0254) as the only factors that were significantly associated with the risk of a second malignant tumor. Three second malignant tumors of the central nervous system occurred following treatment with a nitrosourea. Successfully treated patients must be carefully followed to identify treatment related malignant tumors at an early stage.

Cells of the JMV Marek's disease (MD) tumor, originally produced by rapid serial passage of MD lymphoma cells in chickens, were characterized to determine whether they were of host or donor origin and to ascertain certain virus-host cell interrelationships. Differences noted in blood group B surface alloantigens between tumor cells and host lymphocytes indicated a probable nonhost origin (i.e., transplantability) of the tumor. JMV spleen tumors contained predominantly large lymphoblasts bearing MD tumor-associated surface antigen. DNA from JMV tumor cell suspensions hybridized significantly with MD virus cRNA, which indicated that JMV cells contained at least a portion of the MD virus genome. No MD virus was rescued from JMV tumors by techniques suitable for rescue of virus from MD lymphomas. The JMV tumor cells were also devoid of MD virus-specific antigens. These properties differed markedly from those of MD lymphoma cells and make the JMV tumor cell a unique, potentially valuable, tool for further study of oncogenic herpesvirus infection and tumor immunity in the chicken.

Even though the role of fetal hyperinsulinemia in the pathogenesis of fetal macrosomia in patients with overt diabetes and gestational diabetes mellitus seems plausible, the molecular mechanisms of action of hyperinsulinemia remain largely enigmatic. Recent indications that hyperinsulinemia “primes” various tissues to the mitogenic influence of growth factors by increasing the pool of prenylated Ras proteins prompted us to investigate the effect of fetal hyperinsulinemia on the activitiy of farnesyltransferase (FTase) and the amounts of farnesylated p21 Ras in fetal tissues in the ovine experimental model. Induction of fetal hyperinsulinemia by direct infusion of insulin into the fetus and by either fetal or maternal infusions of glucose resulted in significant increases in the activity of FTase and the amounts of farnesylated p21 Ras in fetal liver, skeletal muscle, fat, and white blood cells. An additional infusion of somatostatin into hyperglycemic fetuses blocked fetal hyperinsulinemia and completely prevented these increases, specifying insulin as the causative factor. We conclude that the ability of fetal hyperinsulinemia to increase the size of the pool of farnesylated p21 Ras may prime fetal tissues to the action of other growth factors and thereby constitute one mechanism by which fetal hyperinsulinemia could induce macrosomia in diabetic pregnancies.

Treatment of neural cells with calix[n]arenes featuring sulphonate moieties and linked to Ag nanoparticles results in reduced reactive species. For Gram+ bacteria there is an inverse correlation between anti-bacterial activity and ROS reduction whereas for Gram- bacteria only calix[6]arenes bearing O-alkyl sulphonate functions act as ROS inhibitors and anti-bacterial agents.