摘要:

AbstractExtracts of an emission sample from wood burning, consisting of particles and volatiles, have been fractionated on an HPLC silica gel column into five fractions of increasing polarity. Nonfractionated samples and the individual fractions have been tested in three different short‐term bioassays: the AmesSalmonellaassay, the sister chromatid exchange (SCE) induction‐test in Chinese hamster ovary cells (CHO), and the cell transformation test on Syrian hamster embryo (SHE) cells.Most of the total activity was found in the volatile part of the sample with all three bioassays, whereas the particle extract had the highest activity per unit mass extracted. The second most polar fraction contained most of the mass and was also highly active in all assays. The most polar fraction was very potent in theSalmonellaassay, but showed only a weak response in the eukaryotic bioassays. Storage of the samples for several months at 0°C revealed that the bacterial mutagens present in the most polar fraction were labile; the mutagenicity was almost totally lost after 1 year's sto

ISSN:0270-3211    

DOI:10.1002/tcm.1770040602

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractThis study was designed to investigate the effect of ether anesthesia in rats, before i.p. injections to induce the mono‐oxygenase enzyme system, on biochemical properties of liver S9 fractions. Aminopyrine N‐demethylase and ρ‐nitroanisole O‐demethylase activity levels, their stability, and lipid peroxidation were determined in S9 fractions after etherization (about 1 min in ether vapor chamber daily for 3 consecutive days, before i.p. injections of Na‐phenobarbital and β‐naphthoflavone) and compared with controls receiving the same injections without etherization. The activities were slightly (but not significatively) enhanced after this treatment, but stability was markedly and significatively greater after 1 h of incubation in the conditions of the liver microsomal assay (+ 14.8% and +74.7%, respectively); lipid peroxidation was strongly and significatively depressed (−76.0%). Etherization sufficient to kill the animals on the 4th day resulted in equally active but less stable S9 fraction enzymes. Dimethylnitrosamine (as a standard premutagen) was assayed with the D7strain ofSaccharomyces cerevisiaeusing S9 fractions obtained from both anesthetized and nonanesthetized rats. According to biochemical data, results obtained with S9 from partially anesthetized rats were comparable with the conventional ones (S9 from nonanesthetized rats). On the contrary, the use of more prolonged ether anesthesia, including one on the day the animals are killed, gives S9 fraction significantly less effective.We conclude that if brief etherizations are used, for i.p. injections only, the S9 fractions obtained are entirely satisfactory and the procedures involved in production are simplified; the additional animal treatment (etherization) mu

ISSN:0270-3211    

DOI:10.1002/tcm.1770040603

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractThe attempt has been made recently to categorize carcinogens into two mechanistic types based on their mechanism of action: genotoxic (capable of reacting with and damaging DNA) and epigenetic (unable to damage DNA to any detectable extent). By requiring that a given chemical fit into one or the other of these narrowly defined categories for regulatory purposes, we are probably oversimplifying potential biological effects. In fact, based on our limited understanding of carcinogenic mechanisms, this artificial distinction should probably be abandoned in favor of a more precise statement of each chemical's mechanism or relative potency of initiating and promoting effects.Since the standard short‐term tests by which carcinogenicity of chemicals is screened were designed to detect certain chemical classes with active electrophilic intermediates, weak or specialized carcinogens may be missed and may be assumed erroneously to be nongenotoxic. The mechanisms of carcinogenicity for such carcinogens may include particulate deposition, active radical formation, liver toxicity, and hormonal interactions. Not all of these secondary mechanisms depend upon a detectable level of binding to DNA, damage to DNA, or modification of the DNA sequence, even though they may demonstrate other characteristics of a complete carcinogen (that is, irreversibility and lack of a threshold).Certain agents have been labeled as epigenetic. However, a consideration of the literature on sample agents (diethylstilbestrol, asbestos, and urethane) reveals that these are not epigenetic carcinogens despite their being labeled as such.Agents with irreversibility and no threshold have initiating potential and, as such, are genotoxic, whereas carcinogens that are classified as nongenotoxic are largely agents that promote the growth of liver tumors. Even promotion can be a mechanistically specialized phenomenon. For example, some promoters are cytotoxic to the liver, but not all liver toxins are liver tumor promoters or liver carcinogens. Further, the carcinogens commonly labeled as epigenetic might cause a unique specialized genotoxicity not detected by common screening tests routinely used for detecting genotoxicity.If we assume that this unrecognized but necessary initiating potential is mediated by some specialized genotoxicity, extra care must be taken to establish a genuine lack of genotoxicity before an agent can be classified (and regulated) as a promoter (lacking the ability to initiate tumor growth but still enhancing tumor development). There is no question that reversible effects with definite thresholds should be evaluated differently from thos that are irreversible and lack a threshold, but the distinction should be based on their effect and potncy, not on their (often unknown) mechanism of genotoxicit

ISSN:0270-3211    

DOI:10.1002/tcm.1770040604

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractThe offspring of mothers with untreated classic phenylketonuria (PKU) have shown a high frequency of microcephaly, mental retardation, pre‐ and postnatal growth retardation, and birth defects. The aim of this study was to determine whether phenylalanine (phe) is the teratogenic agent in maternal PKU.To observe the direct effects of phe on organogenesis, embryos of 9.5‐day pregnant rats were cultured for 48 h in the presence of phe at concentrations of 0.1 to 6.0 mM. Within this range no morphological abnormalities occurred in exposed embryos, when compared to control embryos. However there was a reduction (P ≤ 0.05) in embryonic protein content and somite number at the highest concentration of phe (6.0 mM). This does not preclude the longer‐term effects of phe at later stages of gestation.To examine phe transport into the embryo in response to elevated serum phe levels,3H‐phe uptake studies were undertaken. These showed that3H‐phe from the culture serum is incorporated rapidly into the free amino acid pools and embryonic protein. At serum concentrations of 1.4 mM or higher, phe saturation occurs in the cellular pools of the embryo. Amino acid analysis of the exocoelomic fluid showed that when embryos were cultured for 48 h in serum containing 3.45 mM phe, the total amino acid concentration was maintained near the control levels (16 mM). Of this, 27% (4.26 mM) was contributed by phe, and all other amino acids, except methionine, were decreased with respect to con

ISSN:0270-3211    

DOI:10.1002/tcm.1770040605

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractThe induction of chromosome aberrations, sister chromatid exchanges (SCE), cytotoxicity, and 6‐thioguanine‐resistant mutation by neocarzinostatin (NCS) in Chinese hamster ovary cells was analyzed. It was observed that within the same concentration range of 0.01–0.1 μ/ml NCS, the drug induced a significant increase in all analyzed end‐points except in SCE frequencies. There was no increase in SCE frequencies even when the cells were treated at the G1/S border in the first cell cycle and when aberrations were observed in the same cell showing a second cycle differential staining pattern. Our study indicates that the cellular damage induced by NCS leads to expression in chromosome aberrations, cytotoxicity, and mutagenicity but not in sister chromatid e

ISSN:0270-3211    

DOI:10.1002/tcm.1770040606

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

摘要:

AbstractMouse embryos were labeled in vivo at 10 1/2–12 1/2 days of gestation with [3H]‐thymidine and subjected to DNA damage using x‐ray, methylmethanesulfonate, or methylnitrosourea. DNA damage and its repair were assessed in specific cell preparations from embryos isolated at intervals thereafter using the highly sensitive method of nucleoid sedimentation, which evaluates the supercoiled state of the DNA. Repair of x‐ray damage was demonstrated using trypsin‐dispersed cells from whole embryos and from homogenized embryonic liver to show the validity of the analytical approach. The effects of the highly teratogenic methylnitrosourea and the much less teratogenic methylmethanesulfonate were compared in the targeted limb buds using equitoxic doses of the two alkylating agents. DNA supercoiling was fully restored after 24 hr in limb bud cells damaged with methylmethanesulfonate, while as much as 48 hr were required for full repair of methylnitrosourea damage. These results demonstrated the feasibility of studying DNA repair in embryonic tissues after damage in vivo and suggest that the potency of methylnitrosourea as a teratogen may be correlated with a prolonged period required for complete repa

ISSN:0270-3211    

DOI:10.1002/tcm.1770040607

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770040601

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1984

数据来源: WILEY