摘要:

AbstractSmokers are exposed to a large number of genotoxic compounds that react with DNA to form covalently bound carcinogen—DNA adducts after metabolic conversion to their biological active form. Using the P32‐postlabeling techniques, tobacco smoke related carcinogen—DNA adducts have been demonstrated in DNA isolated from human placenta and umbilical cord vein and artery obtained from 11 nonsmoking and 8 smoking normal healthy women and foetuses. The adduct level was significantly higher in tissues from smokers than from nonsmokers (P= 0.021), when all tissues were combined. Furthermore, the total adduct level was higher in maternal tissue than the level in fetal tissues (P= 0.030). The adduct level in umbilical cord vein DNA was significantly lower than in placenta, and marginally lower than in umbilical cord artery from the same donor. This suggests that the foetus can metabolise some of the genotoxic compounds found in tobacco smoke to DNA‐binding metabolites. The presence of DNA adducts in foetal tissues is indicative of potential genomic damage, that may result in an increased risk for the development of serious diseases, like cancer in childhood or later during the life span of the individual. © 1992 Wiley

ISSN:0270-3211    

DOI:10.1002/tcm.1770120202

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe effects of altering glutathione (GSH) levels in the male reproductive tract have been studied in an attempt to establish a link between chemical‐induced perturbations in glutathione and susceptibility of spermatozoa to chemical insult. Tissue GSH levels were enhanced by a treatment regimen of N‐acetylcysteine (NAC) (250 mg/kg, 4 treatments at 2 h intervals). With this treatment, GSH levels in liver, testis, caput epididymis, and cauda epididymis were elevated to 126%, 110%, 178%, and 136% of control values. Sexually mature male rats were then treated with NAC and challenged with a dose of EMS (100 mg/kg) to determine if enhanced tissue GSH would protect against EMS‐in‐duced dominant lethal mutations. Pretreatment with NAC significantly decreased the post‐implantation loss from 7.05 ± 0.57 with EMS alone to 5.28 ± 0.47. Conversely, a dominant lethal assay was conducted using different doses of phorone pretreatment to determine the relative contribution of hepatic versus reproductive tract GSH in protecting against EMS‐induced dominant lethal resorptions. Doses of 100 mg/kg and 250 mg/kg phorone significantly lowered both hepatic and reproductive tract GSH while 25 mg/kg lowered only hepatic GSH. These three dose levels were used as pretreatments in a dominant lethal study followed by a challenge administration of EMS (50 mg/kg), which is a threshold dose of EMS for producing dominant lethal mutations. Comparison against controls demonstrated a significant potentiation of fetal resorptions in all groups receiving phorone pretreatment, including the 25 mg/kg pretreatment group which only lowered hepatic GSH prior to EMS challenge. The results of these experiments indicate that GHS reserve in the male reproductive tract are insufficient to protect developing spermatozoa from damage by alkylating agents in the absence of hepatic GSH. © 1992 W

ISSN:0270-3211    

DOI:10.1002/tcm.1770120203

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

年代:1992

数据来源: WILEY

摘要:

AbstractThe present experiment was undertaken to investigate possible synergism in induction of rat prostate tumor. F344 rats were repeatedly administered the prostate carcinogens 3,2′ ‐dimethyl‐4‐aminobiphenyl (DMAB), N‐nitrosobis(2‐oxopropyl)amine(BOP), and N‐methylnitrosourea (MNU) sequentially or together at times of hormonal castration induced regenerative cell proliferation of prostate epithelial cells. Group 1 animals received two 100 mg/kg doses of DMAB, two 20 mg/kg applications of BOP, and two times 15 mg/kg of MNU. Groups 2,3, and 4, respectively, received each of the carcinogen treatment alone. Group 5 was given 6 applications of all three in combination, each at one‐third the dose administered to the other groups. The results showed a clear synergism in enhanced tumor development in the colon but not in the prostate, in which the incidence of lesions induced by the three carcinogens was similar to that with DMAB alone. © 1992

ISSN:0270-3211    

DOI:10.1002/tcm.1770120204

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

年代:1992

数据来源: WILEY

摘要:

AbstractIt has been reported that environmental chemicals are important factors in terms of both development and prevention of human cancer. For the latter, detection of early stages is an essential first step followed by clinical trials for surveying populations at risk. Thus a great deal of attention has been focused on these areas. However, investigations of possibilities for active prevention of cancer development itself form another major project. Chemoprevention of carcinogenesis, which means prevention of carcinogenesis by exogenous chemical compounds, has been investigated extensively in a variety of organs in animal models. Usually attention is concentrated on only one organ. However, antioxidants, such as BHA, exert very different effects on different organs, suggesting the necessity of whole body approaches to the question of chemoprevention. Furthermore, the mechanisms of chemoprevention, including the step of carcinogenesis, i.e., initiation, promotion, progression or whole carcinogenesis steps, in which exogenous compounds exert their protective effects, should be considered.A medium‐term bioassay system and a multi‐organ carcinogenesis system, which can be used for investigation of potential for cancer chemoprevention, have been developed in our laboratory. Dose dependent inhibitory effects were established for both BHA and α‐tocopherol in the medium‐term bioassay system, and inhibition of small intestinal carcinogenesis by catechins in green tea has also been investigated in our multi‐organ carcinogenesis protocol. It is extremely important for prevention of human cancer that we find new candidates for chemopreventive agents using animal studies.This paper reviews published reports on chemoprevention, taking into account effective stage, and proposes suitable experimental animal models for future investigations in this increasingly important area. © 1992 Wile

ISSN:0270-3211    

DOI:10.1002/tcm.1770120205

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

年代:1992

数据来源: WILEY

ISSN:0270-3211    

DOI:10.1002/tcm.1770120201

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

年代:1992

数据来源: WILEY