Genotoxic changes in the pulmonary alveolar macrophages of mice, rats and hamsters treated with tobacco smoke.

To determine whether tobacco smoke (TS) is genotoxic for lung tissue macrophages (pulmonary alveolar macrophages, PAM) as a general result of its inhalatory action BD6 rats, Syrian golden hamsters and BDF1 (C57BlxDBA2) mice were subjected to wholebody exposure for 90 or 60 min daily (600 cm3 mainstream smoke in 16-1 glass chamber, 9 or 6 exposures of 15 min each, respectively), for different periods ranging up to 30 days. A significant enhancement of the frequency of polynucleated macrophages (BiN PAM) was observed in all animal species after more than 10-days of repeated exposure to TS. The increased level of BiN PAM (the number of bi- (+) poly-nucleated PAM) correlates with the duration of exposure to TS: on day 20 after the start of inhalation, more than 25/1000 of mice PAM were polynucleated, while on day 30 this applied to approximately 50/1000. Furthermore, a highly significant increase in the level of micronucleated PAM (MN PAM) was also established after 10 days TS treatment of mice and persisted to the end of these examinations. TS was effective in enhancing the micronucleated and polynucleated PAM levels in hamsters irrespective of their sex, as it was in male BD6 rats aged 2 or 11 months. It appears that TS induces a more pronounced elevation of polynucleated PAM frequency in rats than in hamsters and mice. These data suggest that inhaled TS is genotoxic in alveolar macrophages in all exposed species of laboratory animals. An attempt was made to trace the possible clastogenic effect of a single i.p. administration of cyclophosphamide (CP, 15 mg/kg) in mice simultaneously in bone marrow and in PAM. A definite clastogenic effect in bone marrow 24 h and 48 h after CP injection and a total absence of changes in PAM from the lungs during the 15-day period after clastogen exposure were established. These data may support the hypothesis of local production of PAM in the lung from their proliferative precursor. The results provide evidence that PAM in laboratory animals are a sensitive and useful target for assessing harmful effects associated with environmental chemical factors that can be inhaled, including TS.

Potentiation by caffeine of the frequencies of micronuclei induced by mitomycin C and cyclophosphamide in young mice.

Employing the micronucleus test in mouse bone marrow and in fetal mouse liver, the possible clastogenicity of caffeine as well as its influence on MMC- and CP-induced micronucleus levels were studied. The treatment of male and female C57Bl or BDF1 (C57Bl x DBA2) mice with caffeine (1 or 3 x 50 mg/kg and 100 mg/kg, s.c.) had no clastogenic effect in mouse bone marrow or in the fetal livers and maternal bone marrow when pregnant mice were injected with caffeine on day 16-17 of gestation. MMC (2.0 mg/kg, i.p.) increased up to 10-30-fold the number of MNPCEs in bone marrow compared to a 3-7 fold elevation of MNPCEs in fetal liver. A similar effect was also established in pregnant mice treated with CP (30 mg/kg, i.p.). No significant sex differences in spontaneous and MMC- or CP-induced MNPCEs levels were established in C57Bl and BDF1 mice. However, a significantly higher spontaneous rate of MNPCEs as well as a better-expressed responsiveness to the clastogenic activity of MMC and CP were established in C57Bl compared to BDF1 mice. The pregnancy had no effect on MMC- or CP-induced clastogenicity although a tendency to a decreased sensitivity to the damaging activity of MMC seemed to be detected in pregnant C57Bl mice compared to virgin female animals. The combined treatment of mice with caffeine (3 x 100 mg/kg) and MMC or CP caused an up to 45-49% potentiation of clastogenesis in the bone marrow of male, female and pregnant female C57Bl and BDF1 mice but not in fetal mouse livers.

Diminished genotoxicity of mitomycin C and farmorubicin included in polybutylcyanoacrylate nanoparticles.

The genotoxic effects of mitomycin C (MMC) and farmorubicin (FR) in a free form and included in polybutylcyanoacrylate nanoparticles (PBCN) were studied employing the Salmonella/microsome mutagenicity assay and the micronucleus test in mouse bone marrow as well as in mouse fetal liver. The data obtained clearly indicated that MMC (0.25-2.00 micrograms/plate) was a strong mutagen in S. typhimurium TA102, while the same concentrations of this compound in PBCN were ineffective in inducing his+ revertant mutations in bacterial cells. A similar total suppression of mutagenic activity of FR (1.0-20.0 micrograms/plate) was registered in S. typhimurium TA98 when the drug was included in PBCN. Furthermore, the incorporation of MMC (2.0 or 4.0 mg/kg, i.p.) into PBCN strongly diminished or even abolished its clastogenic activity in the bone marrow of virgin and pregnant mice as well as in mouse fetal liver, respectively. In addition, a lack of genotoxic effect of PBCN only was also established. The toxic activity of MMC in mouse bone marrow was significantly reduced or completely abolished after its inclusion in PBCN. A conclusion might be drawn that the genotoxic activity of some antitumor drugs might be markedly diminished or even abolished after their incorporation in PBCN.

[Histological and electron microscopic research on pale, soft, watery and pale, soft pork]. / Khistologichni i elektronnomikroskopski izsledvaniia na bledo, meko, vodnisto i bledo, meko svinsko meso.

Histologic and electron-microscopic studies were carried out on pale-soft-exudative (PSE) and pale-soft (PS) swine meat taken from musculus longissimus thoracis et lumborum. PSE meat was shown to have more strongly manifested morphologic changes. Histologically, with some of the samples there were 'gigantic fibers', their dia exceeding several tens of times the dia of fibers taken from control animals. The electron microscopy with some of the samples revealed a strong deformation of the myofibrils (extensions alternating with narrowings), broader Z-bands, loss of striation in the anisotropic zones, confluence of myofibrils in individual portions, granular destruction or fragmentation of sarcoplasm with swollen or disrupted mitochondria in it, strongly disrupted or destructed Z-bands, lysed or hyperchromic nuclei of the fibers, etc. In PS meat the same ultrastructural changes were observed, although they were less strongly manifested. With such meat some of the samples showed total destruction of the Z-bands, which had led to the full separation of sarcomeres (a phenomenon observed for the first time). These results constitute a contribution to the knowledge of the mechanism through which the PSE meat phenomenon occurs and the evaluation of such meat for consumption.

[Lipid peroxidation in the muscles of various animals]. / Prekisno okisliavane na lipidite v muskuli pri razlichni zivotni.

The dynamics of cumulation was followed up of the products of peroxide oxidation of lipids (POL) during the storage of meat obtained from broiler birds, pigs, and calves, and the activity was determined of one of the systems responsible for the deposition of such products--the nonenzyme system. Results showed that the cumulation of POL products in sampled white poultry meat and meat of pigs and calves, stored for 20 days at -5 degrees to -10 degrees C had close values. The rate of deposition in red poultry meat appeared to be several times higher. Investigations into the activity of the nonenzyme system that produced catalytic effects with POL 4 to 5 hours after sampling the meat revealed that it was lowest in homogenates of calf meat, and it was highest in homogenates of poultry meat, especially of red poultry meat. In this respect the meat of pigs ranked second. The data of the two criteria used showed that the rate of POL in PSE meat was lower than in normal meat of pigs.

[The testing for carcinogenicity of a polyethylene terephthalate vascular prosthesis]. / Testirovane na kantserogennost na polietilentereftalova sudova proteza.

A long-term for possible carcinogenicity was conducted by subcutaneous implantation of 1 cm 2 pieces of polyethylenetherophthalate vascular grafts (PET-VG) to 150 BDF1 mice and 120 Syrian golden hamsters of either sex. A false operation was carried out in the same number of animals of control groups. Implantation was performed in nine-week-old animals. The observation period was 73 weeks for mice and 82 weeks for hamsters. A total of 161 tumors (81 in the experimental group) with 15 localizations were observed in mice and 43 tumors (20 in the experimental group) with 13 localizations--in hamsters. No pathological or statistical evidence of induction of tumors by PET-VG was found. It is concluded that under the conditions of this study PET-VG is not carcinogenic for BDF1 mice and Syrian golden hamsters of either sex.