PubMed Health⌕ Search

Biomedical subjects

M J Zeilmaker

Publications and source records attributed to M J Zeilmaker.

9 recordsLinked to original sources
PubMed2006

Carry-over of dioxins and PCBs from feed and soil to eggs at low contamination levels-- influence of mycotoxin binders on the carry-over from feed to eggs.

Laying hens were fed with compound feed containing six different levels of dioxins, dioxin-like PCBs and indicator PCBs for a period of 56 days. This was followed by a period of 56 days on clean feed. Dioxin levels in feed varied from background levels to three times the current EU tolerance limit of 0.75 ng TEQ/kg. At all dose levels a rapid increase was observed in the dioxin levels in eggs. There was a clear linear dose-response relationship between the dioxin levels in eggs and feed. The feed containing 0.4 ng TEQ dioxins per kg resulted in egg levels just above the EU limit of 3 pg TEQ/g fat. Dioxin-like and indicator PCB residues followed a pattern very similar to that of dioxins. Exposure to the highest indicator PCB level of 32 microg/kg resulted in egg levels around 300 ng/g fat. Exposure to dioxins through contaminated soil, mixed at 10% into the feed, resulted in a similar carry-over as from feed. Mycotoxin binders, mixed at 0.5% into the feed, had little effect on the carry-over of dioxins from the feed to the egg. It can be concluded that consumption of feed or soil with even moderate levels of dioxins and dioxin-like PCBs rapidly results in increased levels in eggs. The current EU dioxin limit for feed cannot guarantee egg dioxin levels below the EU-limit.

Abdomen↗
PubMed2006

A toxicokinetic model for the carry-over of dioxins and PCBs from feed and soil to eggs.

A mathematical model for the kinetics of carry-over of dioxins and dioxin-like PCBs from feed mixed with contaminated oil to eggs has been developed. This model incorporates uptake of the compounds over the gut wall and their subsequent transport by blood, distribution over the body, hepatic metabolism and excretion through egg yolk fat. The model is analysed with respect to the possibility of identifying as yet unknown model parameters by fitting these to the experimental data. The model was fitted to the experimental data on the carry-over from feed to eggs. The calibrated model was applied to calculate the steady-state concentrations in eggs which were compared to European Maximum Residue Levels for dioxins in feed and eggs, showing that these limits do not match. The feed limit of 0.75 ng TEQ/kg should be reduced to about 0.17 ng TEQ/kg in order to guarantee egg levels below the residue limit of 3 pg TEQ/g fat. Experimental results of carry-over from contaminated soil were used to estimate the absorption of dioxin-like compounds from soils as compared to the absorption from feed, resulting in a value around 40 to 60% absorption from soil as compared to around 90% absorption from feed.

Absorption↗
PubMed1991

Mutational specificities of environmental carcinogens in the lacl gene of Escherichia coli H. V: DNA sequence analysis of mutations in bacteria recovered from the liver of Swiss mice exposed to 1,2-dimethylhydrazine, azoxymethane, and methylazoxymethanolacetate.

The host-mediated assay (HMA) was used to determine the spectra of mutations induced in the lacl gene of Escherichia coli cells recovered from the livers of Swiss mice exposed to the carcinogens 1,2-dimethylhydrazine (SDMH), azoxymethane (AOM), and methylazoxymethanolacetate (MAMA). These spectra were further compared with changes induced by dimethylnitrosamine (DMNA) in the HMA methodology. A total of 177 independent lacl mutations arising in the HMA following exposure to SDMH, AOM, and MAMA were analyzed. Single-base substitutions accounted for 97% of all mutations analyzed. The vast majority of the single-base substitutions consisted of G:C----A:T transitions (94% of all mutations). The remaining mutations consisted of A:T----G:C transitions (3% of all mutations) while non-base substitutions accounted for only 3% of the total mutagenesis. The latter mutations consisted of one frameshift mutation and four lacO deletions. The distribution of G:C----A:T transitions induced by the three chemicals in the first 200 bp of the lacl gene was not random, but rather clustered at sites where a target guanine was flanked at the 5' site by a purine residue.

1,2-Dimethylhydrazine↗
PubMed1991

Evaluation of the DNA-repair host-mediated assay. III. Relationship between metabolic activation of dimethylnitrosamine and organ-specific differential lethality induced in E. coli indicator strains.

In the present study the sensitivity of differential lethality as an endpoint for monitoring the presence of organ-specific genotoxic factors within the DNA-repair host-mediated assay (HMA) was determined. The induction of differential lethality in chemically exposed animals was assessed by measuring the recovery ratio Q, i.e., the relative survival of a repair-deficient E. coli K-12 derivative in comparison with its repair-proficient counterpart. Using untreated animals the interindividual fluctuation of the recovery ratio Q was first quantified and then used to determine the level below which it could be considered indicative of chemically induced differential lethality. This Q value was found to be 0.65 or lower. Using this criterion, a significant decrease of the Q value was observed in mice exposed to DMNA at a dose level as low as 15-30 mumole/kg, i.p. Inter-organ transport (liver----extrahepatic organs) of indicator bacteria was studied in reconstruction experiments using the direct-acting methylating agent MNU. These studies showed that inter-organ transport of indicator bacteria did not interfere with MNU-induced differential lethality. Time-related experiments were used to study the effects of inter-organ transport of genotoxic DMNA metabolites. In these studies significant, time-related differences were found in the induction of differential lethality in various organs of mice treated with DMNA. At a dose level of 200 mumole/kg (i.p.) genotoxic factors appeared within 25 min after administration in the liver. In the lungs and kidneys such factors appeared at a substantially slower rate, e.g., 20-120 min after DMNA administration. In persistence experiments differential lethality reached a maximum 30 min after DMNA treatment. No residual effects were detected 60 min after the injection of the carcinogen. These experiments showed that DMNA-derived genotoxic factors diffused from the liver into the bloodstream. The diffusion of these reactive species followed by their transport via the bloodstream to the lungs accounted for maximally 50% of differential lethality observed in bacteria recovered from the latter organ. In contrast, no indications were found for the transport of genotoxic DMNA metabolites from the liver via the bloodstream to the spleen and the kidneys. These results show that organ-specific effects observed in the DNA-repair HMA procedure after DMNA exposure can be primarily attributed to in situ metabolism, rather than diffusion of genotoxic metabolites from the liver to extrahepatic organs.

Animals↗
PubMed1990

Preventive action of thioethers towards in vitro DNA binding and mutagenesis in E. coli K12 by alkylating agents.

Thioethers are effective scavengers of electrophilic metabolites derived from the hepatocarcinogen N-hydroxy-2-acetylaminofluorene (van den Goorbergh et al., 1987). In this study 2 of these thioethers, 4-(methylthio)benzoic acid (MTB) and its methylester, methyl 4-(methylthio)benzoate (MMTB), have been tested for their ability to prevent in vitro DNA binding and mutation induction in E. coli K12 by the direct alkylating agents ethylnitrosourea (ENU), methylnitrosourea (MNU), ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS). In addition to MTB and MMTB, the thioether L-methionine (Met), and the thiols glutathione (GSH) and L-cysteine (Cys) were included for reasons of comparison. MTB was able to (partially) prevent DNA binding and mutation induction by ENU. However, this thioether was ineffective with EMS. DNA binding and mutagenesis by EMS were (partially) prevented by GSH and Cys, while these thiols could not prevent DNA binding and mutation induction by ENU. MMTB was unable to prevent mutation induction by these ethylating agents. With the methylating agents, similar effects of MTB were observed: MTB effectively prevented mutation induction by MNU while it was much less effective towards MMS. GSH and Cys were comparably effective as antimutagenic agents towards both methylating agents. Met was unable to prevent either DNA binding or mutation induction by these agents. Taken together, the results show that aromatic thioethers are able to trap genotoxic electrophiles derived from the nitrosoureas ENU and MNU, and may therefore act as potential anticarcinogens towards these agents, which are only poorly detoxified by GSH.

Alkylating Agents↗
PubMed1989

Mutational specificities of environmental carcinogens in the lacl gene of Escherichia coli. II: A host-mediated approach to N-nitroso-N,N-dimethylamine and endogenous mutagenesis in vivo.

An intrasanguineous host-mediated assay was used to determine the mutational specificity of the hepatocarinogen N-nitroso-N,N-dimethylamine metabolized in vivo. A total of 114 forward mutations in the lacl gene of Escherichia coli reisolated from the livers of treated Swiss albino mice were characterized at the DNA sequence level. Consistent with the methylating ability of this compound and the demonstrated mutagenic specificity of O6-methylguanine, the predominant mutation was the G:C----A:T transition. These were recovered, on average, seven times more frequently at guanines flanked (5') by a purine residue than at those preceded by a pyrimidine residue--a specificity similar to that reported for many direct-acting SN1 alkylating agents. This nitrosamine appears to be distinguished from related N-nitroso methylating compounds by the induction of additional mutational events. Here, the exceptions consisted of four A:T----G:C transitions, four A:T site transversions, and a single G:C----T:A transversion. In addition, the DNA sequence alterations of 34 I- mutants of E. coli reisolated from otherwise untreated mice were identified. The predominant mutation was the G:C----A:T transition, which accounted for almost half of all background mutations. The sites at which these mutations were recovered appear to indicate that some of these mutations may have arisen as a result of an accelerated rate of cytosine deamination. These data suggest that many of the additional "spontaneous" mutations observed under in vivo conditions resulted from genotoxic events occurring during the host-defense (immune) reaction.

Animals↗
PubMed1986

Inhibition of junctional intercellular communication as a possible short-term test to detect tumor-promoting agents: results with nine chemicals tested by dye transfer assay in Chinese hamster V79 cells.

In an attempt to establish an in vitro short-term test to detect tumor-promoting agents, we studied the effects of these agents on junctional intercellular communication in cultured Chinese hamster V79 cells using a microinjection-dye transfer technique. When Lucifer Yellow CH solution is injected into a cell, the average number of cells that become fluorescent after 10 min is 11.6 +/- 7.8 (SD). When the phorbol ester 12-O-tetradecanoylphorbol-13-acetate was used as a positive control, the extent of dye transfer was reduced to 2.9 +/- 2.1 cells within 2 h after incubation with 12-O-tetradecanoylphorbol-13-acetate (100 ng/ml). Nine chemicals that have been reported to have or suspected of having tumor-promoting activity in experimental animals were tested at different doses and after different incubation times. 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane, lindane (1,2,3,4,5,6-hexachlorocyclohexane), phenobarbital, and butylated hydroxyanisole showed inhibitory properties in V79 cells, but with kinetics different from that of 12-O-tetradecanoylphorbol-13-acetate. With 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane and lindane, exposure for 24 h resulted in full blockage of dye transfer; with phenobarbital, a treatment time of 96 h was necessary to achieve this effect, and butylated hydroxyanisole was more active after 48 h than after 24 or 72 h incubation. Five of the reported or suspected tumor-promoting agents, benzoyl peroxide, anthralin, deoxycholic acid, lithocholic acid, and butylated hydroxytoluene, had no effect on communication between V79 cells at noncytotoxic doses; deoxycholic acid, lithocholic acid, and butylated hydroxytoluene but not anthralin inhibited communication only at cytotoxic doses. Our results indicate that we can detect several, but not all, types of tumor-promoting agents, using microinjection-dye transfer assay of junctional communication between Chinese hamster V79 cells.

Animals↗