xthA- Escherichia coli, which are missing a major cellular apurinic/apyrimidinic (AP) endonuclease, are 5- to 10-fold more sensitive than xthA+ bacteria to mutagenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) under conditions that induce the "adaptive response." The xthA(-)-dependent mutations are also dependent on SOS mutagenic processing and consist of both transversion and transition b...

The isolation and characterization of streptozotocin (STZ)-induced mutations in the phage P22 mnt repressor gene is described. Cells carrying the plasmid-borne mnt gene were exposed to STZ to give 10-20 percent survival and at least an eleven-fold increase in mutation frequency. DNA sequence analysis showed that 50 of 51 STZ-induced mutations were GC to AT transitions, and one was an AT to GC t...

In the current study, we examined the protective effect of hydroferrate fluid MRN-100 against the carcinogen methylnitronitrosoguanidine (MNNG)-induced gastric and esophageal cancer in rats. MRN-100 is an iron-based compound composed of bivalent and trivalent ferrates. At 33 weeks post treatment with MNNG, rats were killed and examined for the histopathology of esophagus and stomach; liver, spl...

Treatment of normal human cells with DNA-damaging agents such as UV light or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) stimulates the conversion of NAD to the chromosomal polymer poly(ADP-ribose) which in turn results in a rapid depletion of the cellular NAD pool. We have studied the effect of UV light or MNNG on the NAD pools of seven cell lines of human fibroblasts either homozygous or hete...

Chronic inflammation has a decisive role in tumorigenesis, particularly in gastric carcinogenesis. The CC chemokine ligand 2 (CCL2), an important inflammatory cytokine, is involved in the initiation, development and progression of various types of cancer. However, the role of CCL2 in gastric cancer remains to be elucidated. The present study demonstrated that recombinant CCL2 stimulation caused...

Resistance of mammalian cells to S(N)1-type methylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) generally arises through increased expression of methylguanine methyltransferase (MGMT), which reverts the cytotoxic O(6)-methylguanine ((Me)G) to guanine, or through inactivation of the mismatch repair (MMR) system, which triggers cell death through aberrant processing of (Me)G/T ...

The susceptibility of healed, experimental gastric ulcers to chemical carcinogenesis was investigated. Slowly healing gastric ulcers were induced by the acetic acid method in the fundic and pyloric gastric mucosae of inbred male Wistar rats. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered in drinking water at a concentration of 50 mg/liter for 360 days after ulcer induction. Twenty...

The widely used drug cimetidine (Tagamet) can be nitrosated in the presence of nitrite and under mild acid conditions to form a compound, nitrosocimetidine (NC), which has a chemical struc ture very similar to those of the mutagens and laboratory carcin ogens W-methyl-W'-nitrc-A/-nitrosoguanidine (MNNG) and methylnitrosourea (MNU). NC has given positive indications in several short-term tests f...

Chemoprotection by diet-derived antioxidants has emerged as a cost-effective approach in preventing genotoxicity and carcinogenicity. In this study, we investigated the protective effects of S-allylcysteine (SAC) and lycopene against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced genotoxicity. Quantification of bone marrow micronuclei and chromosomal aberrations in male Wistar rats was use...