Inhibitory effects of freeze-dried milk fermented by selected Lactobacillus bulgaricus strains on carcinogenesis induced by 1,2-dimethylhydrazine in rats and by diethylnitrosamine in hamsters.

Fermented milk products might be used for cancer chemoprevention due to their putative anticarcinogenic and antitumor activities. The diet was supplemented with freeze-dried milk fermented by Lactobacillus bulgaricus strain LBB.B 144 (product FFM.

DNA alterations in rat organs after chronic exposure to cigarette smoke and/or ethanol ingestion.

In spite of the epidemiological evidence supporting a synergism between alcohol consumption and cigarette smoking in the pathogenesis of cancers of the aerodigestive tract, there is a paucity of experimental studies evaluating the effects of these agents under well-controlled conditions and exploring the mechanisms involved. We exposed groups of female BD6 rats, aged 8 months, to ethanol (5% in drinking water for 8 consecutive months) and/or whole-body to mainstream cigarette smoke (1 h/day, 5 days/week for 8 months). DNA was purified from different organs and analyzed for the presence of DNA-protein crosslinks and 32P-postlabeled DNA adducts after butanol enrichment.

Modulation of diethylnitrosamine carcinogenesis in rat liver and oesophagus.

A series of 16 experiments, using a total of 2,000 BD6 rats, was designed in order to assess the ability of 8 individual agents or their combinations to modulate the liver and oesophageal carcinogenesis induced by multiple doses of diethylnitrosamine (DEN). Of the antioxidants tested, sodium selenite, ascorbic acid, and butylated hydroxytoluene generally exhibited protective effects on both types of tumors. In contrast, retinoic acid behaved as a promoter of DEN hepatocarcinogenesis, but this effect could be eliminated by its combination with either selenite or butylated hydroxytoluene.

Modulation of the mutagenic activity of cigarette smoke, cigarette smoke condensate and benzo[a]pyrene in vitro and in vivo.

A series of naturally occurring compounds were tested for the ability to modulate the mutagenicity induced by cigarette smoke (CS), cigarette smoke condensate (CSC) and benzo[a]pyrene (BP) in the Salmonella/microsome mutagenicity assay and the micronucleus test in mouse bone marrow. Sodium selenite, retinol acetate and alpha-tocopherol significantly decreased the mutagenic activity of CS in Salmonella typhimurium TA98. Ascorbic acid, reduced glutathione (GSH), cysteine, caffeine, theophylline, cobalt chloride, folic acid, adenine, adenosine, guanosine, cytidine and cytosine were conversely devoid of any significant effect.

Coclastogenicity of ethanol with cigarette smoke in rat erythroblasts and anticlastogenicity in alveolar macrophages.

A series of experiments was carried out to assess cytotoxic and cytogenetic effects in bone marrow polychromatic erythrocytes (PCE) and pulmonary alveolar macrophages (PAM) resulting from individual or combined exposure of male BD6 rats to ethanol, cigarette smoke and Aroclor 1254. Addition of 5% ethanol to drinking water did not affect the micronucleus frequency but consistently enhanced the proportion of polynucleated PAM. Moreover, the higher concentration used (10%) was cytotoxic in the bone marrow.

Effect of metabolic inhibitors, methylxanthines, antioxidants, alkali metals, and corn oil on 1,2-dimethylhydrazine carcinogenicity in rats.

The effect of the oral administration of 10 compounds on 1,2-dimethylhydrazine (DMH) carcinogenesis was investigated in 180 male Wistar rats and 510 male BD6 rats. DMH, administered s.c.

Clastogenic activity of urethane in mice.

Single intraperitoneal (i.p.) treatment of male and female BDF1 (C57B1 x DBA2) mice with urethane (0.

Modulation of genotoxic activity of tobacco smoke.

Tobacco smoke (TS) caused a three- to nine-fold increase in the frequency of his+ revertants in Salmonella typhimurium TA98 but not in TA97a, TA100 or TA102. Activation by a post-mitochondrial fraction obtained from the liver of rats pretreated with Aroclor-1254 or methylcholanthrene was required; fractions from phenobarbital-pretreated or untreated rats had no effect. Vitamins A and E, but not ascorbic acid, inhibited the TS-induced mutagenesis by up to 63%, whereas glutathione and cysteine increased it slightly.

The mutagenic and clastogenic activity of tobacco smoke.

Employing the Salmonella/microsome mutagenicity assay it was established that the mutagenic effect of tobacco smoke (TS) (240 cm3 in a 16-l glass chamber, at 1 min or 5 min exposure time) in S. typhimurium TA98 depended on the type of S9 mix used. Addition of S9 mix obtained from the liver of 3-methylcholanthrene- or Aroclor-1254-pretreated rats but not from the liver of phenobarbital-pretreated or untreated rats was required to demonstrate the mutagenic activity of TS.

Investigation of the mutagenic activity of tobacco smoke.

The genotoxic effect of whole tobacco smoke was studied employing the Salmonella/microsome mutagenicity assay, the micronucleus test in mouse bone marrow and UDS in peripheral human lymphocytes. It was established that tobacco smoke (120-480 cm3 in a 16-1 glass chamber, at 1-10 min exposure time) induced a 3-9-fold increase of spontaneous his+ reversion mutation rate in S. typhimurium TA98, but not in strains TA97a, TA100 and TA102.

The effect of antioxidants on MNNG-induced stomach carcinogenesis in rats.

The effect of vitamins A, C and E, butylated hydroxytoluene (BHT) and glutathione (GSH) on gastric carcinogenesis induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was investigated. Male and female BD-VI rats 2-3 months old received a single oral application of MNNG dissolved in corn oil. The male rats were divided into four groups: Group-I: MNNG 250 mg/kg by intubation; Group-II: MNNG + vitamin C daily in the drinking water (400 mg/l); Group-III: MNNG + vitamin C (400 mg/l) + 100 g of milk broth (for each of 10 rats) containing vitamin A (40,000 IU), vitamin E (0.