On the maternal transfer of 4-aminobiphenyl in rats.

The potential for 4-aminobiphenyl (4-ABP) to be transferred from circulating blood into the milk of lactating Sprague-Dawley rats was determined. The distribution of 14C-labeled 4-ABP into milk was examined at time intervals of less than 1, 20, 60, 120, 240 and 480 min after i.v. dose administration. Elimination of radioactivity from blood and milk was determined to be biphasic. The levels of 4-ABP and/or metabolites were lower in milk than in blood at all time points examined. The levels of radioactivity detected in blood declined less rapidly than in milk. That is, the percent of the dose per ml of blood declined from 0.81-0.45, while the percent of the dose per ml of milk declined from 0.38-0.06 during the 8 h time period. The radioactivity present in milk was partially extractable with ethyl acetate with 43% of the radioactivity being extractable at the earliest time point while only 16% was extractable after 8 h. The level of radioactivity associated with the protein precipitate of the milk samples increased from 4-21% within 4 h after treatment. The potential of 4-ABP or its metabolites to exert a genotoxic effect on newborn pups via maternal transfer was also examined. Dams were treated on day 1 post partum and then daily with 4-ABP (10 mg/kg) in corn oil or corn oil alone for 2 weeks. Each experimental group had four liters of pups each containing 5 pups. Pups were sacrificed at 15 days of age, separated by sex and the levels of 4-ABP:DNA adducts in liver determined using 32P-postlabeling. DNA adduct profiles were similar between male and female pups with total adduct levels of 332 and 338 fmol of adducts/mg of DNA, respectively. These results indicate that the genotoxic effects of 4-ABP can be transmitted from exposed dams to the nursing offspring.

Significant increase of IQ-type heterocyclic amines, dietary carcinogens in the plasma of patients with uremia just before induction of hemodialysis treatment.

The concentrations of 2-amino-3-methylimidazo(4,5-f) quinoline (IQ) and 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx), a family of mutagenic and carcinogenic heterocyclic amines, in the plasma of normal subjects (10 cases), patients with uremia receiving maintenance hemodialysis treatment (9 cases) and patients with uremia just before induction of hemodialysis treatment (5 cases) were determined by a high-performance liquid chromatography method. The plasma levels of IQ and MeIQx in uremic patients just before induction of hemodialysis treatment were 12.6 +/- 4.1 nM (mean +/- S.D., n = 5) and 10.0 +/- 2.3 nM (n = 5), respectively. In patients with uremia receiving maintenance hemodialysis treatment, IQ and MeIQx were detected in 4 and 2 out of 9 cases, respectively and the levels of those in the plasma were 4.1 nM (n = 4) and 1.7 nM (n = 2), respectively. However, IQ and MeIQx could not be detected in all normal subjects. These results indicate that uremic patients just before induction of hemodialysis treatment are actually exposed to higher levels of the carcinogenic heterocyclic amines, as compared with normal subjects and uremic patients receiving maintenance hemodialysis treatment.

Modified mutagen metabolism in Schistosoma hematobium-infested organisms.

The relationship between parasite infestation and chemical mutagen metabolism was investigated in this study. Schistosoma hematobium, long associated with increased incidence of bladder cancer in humans, was chosen as a model parasite. Urine samples, serum samples, and liver tissue extracts (S-9) from infested and control hamsters were used with the Ames Salmonella/microsome test to follow 3,3'-dichlorobenzidine (DCB), aflatoxin B1 (AFB1), and 2-acetylaminofluorene (AAF) mutagenicity. Liver S-9 preparations from infested and control hamsters showed little difference in activation potential for DCB and AFB1. Aroclor 1254-induced rat liver S-9, however, was remarkably efficient at reducing the mutagenicity of DCB. This process was reversible by beta-glucuronidase (BG). Studies on infested and control hamsters indicated increased BG activity in serum and urine. Urine concentrates (UC) from infested and control animals were not mutagenic by themselves, but did enhance the mutagenicity of AAF and DCB in the presence of S-9 and BG. Urine concentrates from infested animals showed greater enhancement of DCB mutagenicity than did UC from control animals. These data suggest that increased BG and unknown urinary factors in infested hamsters play a role in altering chemical mutagen activity.

Binding of chemical carcinogens and mutagens to rat hemoglobin.

The alkylation of hemoglobin is a proposed dose monitor for chemical carcinogens and mutagens. The binding of fifteen chemical carcinogens and mutagens to rat hemoglobin was determined. Direct acting carcinogens and indirect acting carcinogens including aromatic amines, halogenated hydrocarbons, nitrosamines, polycyclic aromatic hydrocarbons, aflatoxin B1 and benzene bound hemoglobin. The efficiency of carcinogen and mutagen hemoglobin was dose dependent and ranged from 0.007 to 2.3% of an oral dose. The binding of chemical carcinogens and mutagens to hemoglobin would appear to be generic so that it could be developed into a dose monitor for a large number of known carcinogens and mutagens.