Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxicology and carcinogenesis studies of ampicillin trihydrate and penicillin VK, two widely used beta-lactam antibiotics, were performed in F344/N rats and B6C3F1 mice. In these studies ampicillin trihydrate was administered for 2 years to rats at doses of 0, 750, or 1500 mg/kg and to mice at doses of 0, 1500, or 3000 mg/kg, and penicillin VK was administered to rats and mice at doses of 0, 500, or 1000 mg/kg. Both drugs were administered by oral gavage in corn oil. Toxic lesions of the stomach were seen in rats and mice after ampicillin trihydrate administration and in mice after penicillin VK administration. In male rats that received ampicillin trihydrate there was a marginal increase in incidence of mononuclear cell leukemia and pheochromocytomas of the adrenal gland medulla. There was no evidence for carcinogenic activity in female rats or male and female mice after ampicillin trihydrate administration or in rats and mice after penicillin VK administration.
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PMID:Two-year toxicity and carcinogenicity studies of ampicillin trihydrate and penicillin VK in rodents. 249 39

The age-specific occurrence of adult T-cell leukemia (ATL) was analyzed using 357 cases collected during nationwide surveys carried out between 1982 and 1985 in Japan. A simple Weibull distribution function fitted well as a model. The mode of ATL onset was log-linear in this model and the curves for males and females overlapped completely. The presence of age-dependent accumulation of leukemogenic events within human T-cell leukemia virus type 1-immortalized T cells was suggested prior to the development of ATL, and the approximate number of independent leukemogenic events in ATL is estimated to be five. This stochastic analysis supported a multi-step carcinogenesis as an appropriate model for ATL.
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PMID:Multi-step carcinogenesis model for adult T-cell leukemia. 249 54

Age-adjusted mortality rates were analyzed to examine the dose-response relation between ingested arsenic levels and risk of cancers and vascular diseases among residents in the endemic area of blackfoot disease, a unique peripheral vascular disease associated with long-term exposure to high-arsenic artesian well water and confined to the southwestern coast of Taiwan. The arsenic levels in well water determined in 1964-1966 were available in 42 villages of the study area, while mortality and population data during 1973-1986 were obtained from the local household registration offices and Taiwan Provincial Department of Health. Age-adjusted mortality rates from various cancers and vascular diseases by sex were calculated using the 1976 world population as the standard population. A significant dose-response relation was observed between arsenic levels in well water and cancers of the bladder, kidney, skin, and lung in both males and females, and cancers of the prostate and liver in males. However, there was no association for cancers of the nasopharynx, esophagus, stomach, colon, and uterine cervix, and for leukemia. Arsenic levels in well water were also associated with peripheral vascular diseases and cardiovascular diseases in a dose-response pattern, but not with cerebrovascular accidents. The dual effect of arsenic on carcinogenesis and arteriosclerosis and the interrelation between these two pathogenic mechanisms deserve more intensive study.
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PMID:Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases. 258 5

Methyl-deficient (lipotrope-deficient) diets enhance liver carcinogenesis in rodents. Although the mechanisms responsible for the cancer-promoting activity of such diets have not been identified, they have been observed to cause impaired immune response, alterations in methylation of liver RNA and DNA, and enhanced susceptibility to oxidative damage. Since alterations in gene expression may also play a critical role, the present studies examined the expression of the c-myc, c-H-ras, epidermal growth factor receptor, and ornithine decarboxylase genes, as well as endogenous retrovirus-like sequences, in C57BL/6J x C3H/HeJ F1 mouse liver during the first 2 weeks of feeding of a methyl-deficient diet. The kinetics of liver cell proliferation was investigated in parallel. Increased [3H]thymidine incorporation into liver DNA was found at day 4 and reached a maximum at days 7-11 after commencement of the methyl-deficient diet, when compared to age-matched mice fed a complete diet. Northern blot analysis of polyadenylated liver RNA samples indicated an increase in the levels of RNA homologous to Moloney murine leukemia virus and intracisternal A particle sequences but no significant change in the level of VL30 retrovirus-related RNA in the samples from mice fed methyl-deficient diets. A marked increase in the levels of c-myc and a slight increase in the levels of ornithine decarboxylase and c-H-ras transcripts were seen in the liver RNA samples from the treated mice. Of particular interest was a decrease in the abundance of epidermal growth factor receptor transcripts in the liver RNA samples from the treated mice. These changes in cellular levels of specific RNA resemble, in several respects, those we have previously described in rodent liver during regeneration and tumor promotion and also those seen in rodent hepatomas. They may reflect, therefore, a common profile of gene expression relevant to cell proliferation.
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PMID:Altered expression of retrovirus-like sequences and cellular oncogenes in mice fed methyl-deficient diets. 266 Sep 81

Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2; greater than 99.7% pure) were conducted in groups of 60 F344/N rats and 60 B6C3F1 mice of each sex for each of three exposure doses and vehicle controls. These composite studies on benzene were designed and conducted because of large production volume and widespread human exposure, because of the epidemiologic association with leukemia, and because previous experiments were considered inadequate or inconclusive for determining carcinogenicity in laboratory animals. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals. For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3F1 mice, and female B6C3F1 mice. In male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. In female rats, benzene caused increased incidences of Zymbal gland carcinomas and squamous cell papillomas and squamous cell carcinomas of the oral cavity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice. 267 95

Epidemiological evidence for prenatal carcinogenesis includes associations between cancer in young people and intrauterine exposure to X-rays, drugs and hormones and prezygotic events such as specific chromosomal aberrations associated with specific cancers. Recent findings suggest that the hormonal environment during early gestation can result not only in the development of clear-cell adenocarcinoma of the vagina but also in the development of germ cell tumours of the testes and ovary. Hormone-related risk factors for testicular germ cell neoplasms include maternal use of exogenous oestrogens during early gestation and, possibly, maternal nausea, maternal obesity and race as well. Ovarian germ cell tumours also appear to be related to maternal use of hormones and obesity. Several epidemiological studies of cancer in young people have been directed towards suggested associations with parental occupational exposures, parental cigarette smoking and household exposures to electric and magnetic fields (EMF). The findings of the many studies of parental occupational exposures are inconsistent and are often nonspecific with respect to the type of childhood cancer and the job exposure implicated. Parental cigarette smoking has been associated in some studies with an increased risk for cancer among children and young adults, and in other studies with an increased risk among mature adults, but the findings are not consistent across studies. Three studies of all types of childhood cancer found risk to be related to household exposures to EMF; in all three, the risk for central nervous system tumours was increased, and in two of the three leukaemia risk as well. A fourth study showed no association between childhood leukaemia and EMF. A hypothesis is proposed which suggests that prenatal and early childhood exposure to N-nitroso compounds (NOC) may be related to the development of primary tumours of the brain in children. Experimentalists have shown that various NOC are potent nervous system carcinogens, particularly when animals are exposed transplacentally. This experimental model and findings from a Los Angeles case-control study (209 pairs) of brain tumours in young people led to the proposed epidemiological hypothesis. Although this and other epidemiological studies of NOC have major limitations, findings from epidemiological studies of congenital defects and of other childhood cancers lend the hypothesis some support. A large international collaborative case-control study of childhood brain tumours was begun recently. This study has a major advantage over most case-control studies in adults because the exposure period of greatest interest (gestation) is clearly defined.
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PMID:Epidemiological studies of perinatal carcinogenesis. 268 Sep 50

Parental exposure to radiation increases the incidence of tumours in resultant F1 offspring. Induced lung tumours are inherited, as they are dominant mutations, indicating that germ line mutation causes cancer in progeny. This finding is now confirmed in three different strains of mice (ICR, LT, and N5). Most of the tumours induced in offspring were transplantable (malignant); furthermore, preliminary experiments reveal involvement of some known and novel oncogenes in these tumours. A germ line mutation causing a tumour ('tumour mutation') is weakly carcinogenic by itself, but it is strongly expressed in the progeny after postnatal treatment with a small dose of the carcinogenesis promoting agent urethane. Tumour yields induced by chemical carcinogens were 20-250 times higher than those induced by tumour mutation alone. Embryonic mutagenesis also causes cancer in offspring. Although radiation in utero at early embryonic stages induces significant yields of somatic mutations, radiation is not or very weakly carcinogenic. However, it induced persistent hypersensitivity to postnatally administered carcinogenic (urethane) and promoting (12-O-tetradecanoylphorbol 13-acetate) agents. The mechanism must be similar to that of germ line mutation in causing tumours. No leukaemia was found in these experiments as in atomic bomb survivors exposed in utero, but all induced tumours were of adult types. The results predicted the recent epidemiological finding that the incidence of adult cancers is now increasing dramatically among atomic bomb survivors exposed in utero.
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PMID:Role of radiation-induced mutations in multigeneration carcinogenesis. 268 Sep 54

To determine if diploid human fibroblasts can be transformed by the N-ras oncogene found in human tumors, early passage cell lines were transfected with an N-ras oncogene from human leukemia cell line 8402 cloned into a high expression plasmid (pSV N-ras), with the N-ras oncogene from human fibrosarcoma cell line HT1080 cloned into pNR-MG1, or with pSV2neo as a control. Each plasmid carries the neo gene coding for Geneticin resistance, but in pSV N-ras, the endogenous promoter of the N-ras gene has been eliminated, and the gene has been inserted between the viral long-terminal repeat (LTR) and the neo gene so that transcription initiated from the LTR must transcribe the N-ras gene before transcribing neo. In pNR-MG1, transcription of the N-ras gene is driven from its endogenous promoter, and the neo gene is transcribed from an SV40 viral promoter, as in pSV2neo. When the transfectants were selected for Geneticin resistance, 70% of the colonies formed with pSV N-ras consisted of morphologically altered cells. Less than 5% of the drug resistant colonies formed with pNR-MG1 had cells with altered morphology, and the change in morphology was much less distinct than with pSV N-ras. No colonies of morphologically-transformed cells were found with pSVneo. If the transfected populations were not selected in Geneticin, but were simply allowed to grow to confluence, very distinct foci composed of morphologically-altered cells could be seen against a contact-inhibited monolayer with pSV N-ras. Foci formed by the pNR-MG1 population were subtle and much less distinct. No foci were found with pSV2neo. Representative colonies and foci of morphologically-transformed cells were isolated. Those from pNR-MG1 transfection reverted to a normal morphology after 5-10 population doublings. Most of those from pSV N-ras transfection either reverted or senesced after 5-10 population doublings. However, progeny of two colonies expressed stable morphological transformation throughout a normal life span equal to that of age-matched pSV2neo controls. Both of these stably transformed cell strains exhibited anchorage independence and formed distinct foci. Immunoprecipitation analysis showed that these cells produced much larger amounts of N-ras protein than did pSV2neo-transfected control cells. However, these two cell strains did not exhibit an infinite life span in culture and were unable to form tumors in athymic mice.
Carcinogenesis 1989 Apr
PMID:Transformation of diploid human fibroblasts by transfection of N-ras-oncogenes. 270 11

An important biological function of glutathione (GSH) resides in the detoxication reactions mediated by enzymes such as glutathione-S-transferase (GSTs) and glutathione peroxidase (GPX). An increasing body of evidence implies that GSH and these enzymes play important roles in determining the sensitivity of tumours against cytotoxic drugs like quinone antibiotics, in particular adriamycin (Adr). In the present study, we have analysed the effects of cell-cycle on GSH and GSH-dependent enzymes in an attempt to explain cell-cycle specificity of these antileukaemic drugs which were shown to be involved in free-radical-type reactions. Determination of GSH, GST, GPX and superoxide dismutase in cell-cycle-enriched fractions of five different human myeloid leukaemia cell lines (KG1, K562, U937, ML-1 and ML-2) yielded results identical to those obtained in random cultures, which implies that neither GSH nor GSH-related enzymes are cell-cycle regulated. These findings argue against the presumption that cell-cycle specificity of cytotoxic drugs like Adr could be due to the glutathione-dependent metabolism in myeloid leukaemia cell lines.
Carcinogenesis 1989 Sep
PMID:Influence of cell cycle on glutathione-S-transferase, selenium-dependent glutathione peroxidase, superoxide dismutase and glutathione levels in human myeloid leukaemia cell lines. 276 62

The expression of moloney murine leukemia virus (Mo-MuLV), intracisternal A particle (IAP), virus-like 30S sequence (VL30), early transposon (ET) endogenous retroviral sequences was analysed in the liver of untreated C3Hf, C57BL/6J and AKR mice, and in the lungs of untreated A/J, BALB/c, C3Hf and C57BL/6J mice. C3Hf mice are genetically susceptible to hepatocarcinogenesis, whereas the other strains are resistant. A/J and BALB/c mice are genetically susceptible to lung carcinogenesis, whereas the other strains are resistant. Both in liver and lung tissues we found differences between murine strains in the pattern of basal retrovirus expression. The effect of inhibition of protein synthesis on the levels of retroviral mRNAs was studied in the same tissues and strains 3 h following in vivo cycloheximide treatment. Cycloheximide treatment increased the liver and lung levels of virus Mo-MuLV, IAP, ET related transcripts in a strain dependent way, whereas VL30 mRNA levels increased in both tissues of all strains examined. These results suggested the existence of labile proteins that regulate the abundance of specific retroviral mRNAs in murine liver and lung in a strain specific fashion. No clear relationships between pattern of retrovirus expression and genetical susceptibility to hepatocarcinogenesis was found. The strains genetically resistant to lung carcinogenesis (C3Hf, C57BL/6J) showed higher lung basal levels and higher cycloheximide inducibility of mRNAs homologous to Mo-MuLV than the susceptible strains (A/J, BALB/c).
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PMID:Cycloheximide increases endogenous retroviral RNA levels in murine liver and lung. 277 73


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