Distributions of cell populations within alpha-particle range of plutonium deposits in the rat and beagle testis

Plutonium is not uniformly distributed in testicular tissues; thus some cell populations may receive larger or smaller radiation exposures than would be expected if the nuclide were uniformly distributed. The distributions of cell populations within alpha-particle range of Pu deposits in rat and beagle testes were determined. The data were collected from autoradiographs of testicular tissues containing 241Pu. A cell distribution factor (CDF) was determined for each cell population and is defined as the average number of each cell type within alpha-particle range of each observed Pu deposit relative to the number of each cell type that would be expected within alpha-particle range of each Pu deposit, if the deposits were distributed uniformly. In addition, the percentage of the spermatogonial stem cell population within alpha-particle range of Pu deposits was determined. In rats, the CDF for the spermatogonial stem cells is about 2.2. This value is similar to other enhancement and inhomogeneity factors reported for rodents in the literature. In beagles the CDFs to all cells in the seminiferous epithelium were less than the rats. In addition, the percentage of spermatogonial cells within alpha-particle range of Pu concentrations in the interstitial tissues was a factor of about 3 less in the dog than in the rat. The largest CDFs seen in both species were in the interstitial tissues, particularly for Leydig cells. Because the organization of testicular tissues in the beagle is quite different from rodents but more similar to human, the results from this study suggest that extrapolations from rodents to humans may tend to overestimate the potential for radiation exposure to spermatogonial stem cells as well as the fraction of the spermatogonial stem cell population at risk to exposure from internally deposited 239Pu.     

Roles of the trkB and trkC gene products of Escherichia coli in K+ transport

Mutations at the trkB and trkC loci of Escherichia coli produce an abnormal efflux of K+. The mutations are partially dominant in diploids and revert frequently by what appears to be intragenic suppression to the null state. The mutations can be reverted by insertion of Tn10 into the mutated gene, and spontaneous revertants are fully recessive to the mutant allele in diploids. K+ efflux produced by NEM* and by DNP* persists in strains with presumed null mutations at either locus, indicating neither gene product is the primary target for the effect of these inhibitors on K+ efflux. The results are consistent with the view that trkB and trkC encode independent systems for K+ efflux. Mutations at these loci alter regulation of the process so that K+ efflux occurs inappropriately. A second mutation to the null state abolishes this abnormal K+ efflux. These genes may encode K+/H+ antiporters, an activity postulated to mediate K+ efflux and demonstrated to exist in E. coli and other bacteria.     

Antitumor properties of vindesine-monoclonal antibody conjugates

Summary The anticancer alkaloid vindesine (VDS) was conjugated to four mouse monoclonal antibodies recognizing human tumor-associated antigens. The antibodies were 96.5 (antimelanoma, IgG2a); 791T/36 (antiosteogenic sarcoma, IgG2b); 11.285.14, and 14.95.55 (anticarcinoembryonic antigen, IgG1 and IgG2a respectively). Conjugates VDS-96.5 and VDS-791T/36 were tested in vitro and shown to be specifically cytotoxic for target cells expressing the appropriate antigen. The in vivo effects of the antibodies and conjugates were tested against human tumor xenografts in athymic or immunodeprived mice using multiple treatments. Conjugate VDS-96.5 retarded the initial growth of a melanoma xenograft, whereas free antibody was without effect. Similarly, VDS-791T/36 but not free antibody retarded the growth of osteogenic sarcoma 791T. The most marked antitumor effects observed were those obtained with VDS conjugates of the anti-CEA antibodies against a colorectal tumor xenograft. Antibody 14.95.55 suppressed tumor growth both alone and as a VDS conjugate, whereas 11.285.14 produced only a slight effect alone but an almost complete and lasting suppression of tumor growth as a VDS conjugate. Free VDS had little effect at nontoxic levels. Acute studies showed that VDS-11.285.14 conjugate was considerably less toxic than free VDS in Balb/c mice.     

Exposure of E. coli to nitrosocimetidine induces the adaptive response to alkylating agents

The cytotoxic and mutagenic properties of nitrosocimetidine (NC), together with its ability to induce the adaptive response DNA-repair pathway were compared with those of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) using Escherichia coli as test organism. MNNG was found to be 250-fold more cytotoxic and 500-fold more mutagenic than NC. Prior cultivation of E. coli in low concentrations of NC protected it against the cytotoxic and/or mutagenic effects of challenge with either NC or MNNG or methyl methanesulphonate (MMS). Induction of the adaptive response by prior cultivation in low concentrations of MNNG reduced the mutagenic and cytotoxic effects of subsequent NC challenge. These results lead us to conclude that although NC is a less potent mutagen than MNNG, the DNA lesions it produces are capable of not only inducing, but also of being repaired by, the adaptive response.     

Dietary fat modifies the in vivo mutagenicity of some food-borne carcinogens

Female BALB/c mice were fed a low fat diet (1% safflower oil, by weight) or one supplemented with 25% (by weight) of beef fat or olive oil. The abilities of these diets to modify the in vitro and in vivo hepatic conversion of the dietary carcinogens aflatoxin B1, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) to bacterial mutagens was evaluated. Dietary olive oil appeared to increase the metabolism of both MeIQ and Trp-P-2 to bacterial mutagens in vivo using the intrasanguineous host-mediated assay. Feeding mice either of the high-fat diets increased hepatic conversion of these two compounds to bacterial mutagens in vitro. Dietary fat had no effect on the metabolism of aflatoxin B1. Subsequent experiments suggested that the in vivo effects of dietary olive oil on MeIQ and Trp-P-2 mutagenesis were due to the induction of hepatic enzyme activities rather than to increased rates of uptake of the carcinogen from the gut-lumen.     

EDU and ozone protection: Foliar glycerolipids and steryl lipids in snapbean exposed to O3

Effects of the antiozonant EDU, N-[2-(2-oxo-1-imidazolidinyl) ethyl]-N'-phenylurea, on the content and composition of foliar lipids in snapbean ( Phaseolus vulgaris L. cv. Bush Blue Lake 290) before and after a single, acute ozone (O₃) exposure were assessed. Pretreatment with EDU conferred protection against O₃-induced necrosis and losses of glycerolipids and chlorophyll. Systemic treatment of snapbean plants with EDU did not significantly alter membrane lipids in the first trifoliate leaf. Leaves of untreated controls had lost ca 50% of both galacto- (GL) and phospholipids (PL) by the end of a 3 h exposure to 0.4 μl l⁻¹ O₃. A decline in the ratio of mono- to di-galactosyldiacylglycerol (MGDG/DGDG) was associated with the loss of GL, and a decline in the ratio of linoleic to linolenic acid (18:2/18:3) was associated with the loss of PL in untreated controls. EDU-treated plants showed no significant loss of foliar GL and PL. The MGDG/DGDG ratio declined only slightly, and the 18:2/18:3 ratio in PL increased during O₃ exposure of EDU-treated seedlings. The level of total membrane sterols, including free sterols (FS), acylated steryl glycosides (ASG) and steryl glycosides (SG), did not change during O₃ exposure of either treated or untreated plants. However, in the controls the proportions of ASG and SG increased at the expense of FS, and the ratio of stigmasterol/sitolsterol increased in FS and SG. In EDU-treated plants, a relatively small increase in SG was offset by a decrease in FS, and there was no change in the stigmasterol/sitosterol ratio in ASG, SG or FS. The results indicate that EDU may confer tolerance to O₃ through induction of enzyme systems involved in the elimination of activated oxygen species and free radicals.