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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Benzene is one of the best studied of the known human carcinogens. It causes leukemia in humans and a variety of solid tumors in rats and mice. Decades of research on benzene metabolism, pharmacokinetics, cytotoxicity, genotoxicity, and carcinogenicity in vivo and in vitro are starting to converge on a small set of overlapping hypotheses about the most probable biological mechanisms of benzene toxicity and carcinogenicity. Although there is still room for surprises, it seems likely that the ultimate answer to the mystery of how benzene exerts its multiple effects will consist of elaborations and extensions of one or more of the current hypotheses. This paper reviews benzene health effects and biology, showing how various aspects of metabolism and cytotoxicity fit together with genotoxic and nongenotoxic effects to help explain how benzene may cause cancer. Its goals are: (i) to introduce the qualitative biological background needed for detailed quantitative dose-response modeling of benzene cancer risks; and (ii) to survey a rapidly evolving area of research that shows promise of producing fundamental insights into the mechanisms of toxicity and carcinogenesis for several chemicals--benzene and perhaps phenols, catechols, and other hydroxylated ring hydrocarbons--in the decade ahead.
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PMID:Biological basis of chemical carcinogenesis: insights from benzene. 194 51

The relationship between mutagenesis and carcinogenesis was investigated in T x HT crossbred mice using diaplacental application of ethylnitrosourea (ENU) at different stages of embryonal development. Mutagenesis was detected by induction of coat color spots, and the carcinogenic response was investigated in a long-term follow-up study of the F1-generation. The animals were particularly sensitive to induction of tumors at the central nervous system (CNS)-skull/vertebra interface (30% and 20% in ENU-treated male and female offspring, respectively, compared with less than 1% in controls). There was a correlation between the appearance of these tumors and the presence of color spots. This correlation was low but statistically significant in female offspring. Three other types of tumors showed a correlation with the presence of coat color spots. Liver tumors were significantly increased in color spot-positive females but unchanged in males. Lung tumors were reduced in color spot-positive males and appeared earlier in color spot-positive females. There was a lower incidence of lymphoma/leukemia in all spot-positive mice. The reduction in tumor incidence beyond the spontaneous rate in spot-positive animals might be caused by a high cytolethal response to ENU in the relevant organs and tissues.
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PMID:Simultaneous induction of mutagenic and cancerogenic effects in T x HT mice with transplacental ethylnitrosourea treatment. 198 33

The inability of cells in culture to grow in medium where methionine is replaced by its metabolic precursor, homocysteine, has been linked to neoplastic transformation and termed 'methionine dependence' or 'methionine auxotrophy'. The present investigation was undertaken to establish the influence of intracellular glutathione level on methionine auxotrophy in different mouse cell lines. A non-transformed, methionine-independent fibroblast cell line with essential normal growth rate in methionine-deficient, homocysteine-supplemented medium (Met-Hcy+), showed only a slight initial lag and then the same growth as control when glutathione was reduced to less than 5% by the glutathione synthesis inhibitor buthionine sulfoximine (BSO). Increasing cellular glutathione by cystamine in a completely methionine-dependent leukemia cell line did not stimulate the cells to proliferate in Met-Hcy+ medium. A partly methionine-dependent transformed fibroblast cell line with reduced capacity to proliferate in Met-Hcy+ medium showed increased growth potential when the cells were depleted of glutathione by a non-toxic concentration of BSO. An even higher growth potential of these cells in Met-Hcy+ medium was obtained by addition of a non-toxic concentration of cystamine, while only a transient increase of glutathione content was observed under these conditions. Both BSO and cystamine increased the fraction of protein-bound cysteine and homocysteine in the partly methionine-dependent cells. These metabolic alterations correlated with the increased ability of these cells to utilize homocysteine for growth. Our results suggest that methionine auxotrophy is a metabolic defect that is not related to the cellular glutathione status, but may be related to the intracellular distribution between free and protein-bound forms of other thiols as cysteine and homocysteine.
Carcinogenesis 1991 Feb
PMID:Modulation of glutathione content and the effect on methionine auxotrophy and cellular distribution of homocysteine and cysteine in mouse cell lines. 199 90

The catalytic activity of the nuclear enzyme poly(ADP-ribose) polymerase (NAD+ ADP-ribosyl transferase, EC 2,4,2,30) is totally dependent upon the presence of DNA strand breaks. Having isolated a full-length cDNA for the polymerase, we have now evaluated the effect of endogenously and exogenously induced DNA strand breaks on the transcriptional control of this enzyme. During retinoic acid or dimethyl-sulfoxide-induced differentiation of HL-60 human leukemia cells, which may involve DNA breaks as well as other changes in chromatin, mRNA levels for the polymerase increased very early and remained high for up to 48 h after which it decreased to pre-induced levels. Polymerase transcript levels did not change, however, during the induction of DNA strand breaks by dimethylsulfate, a variety of other alkylating agents, X-irradiation, or UV-irradiation in several mammalian cell lines. It appears that in sharp contrast to the catalytic requirement of the polymerase, the induction of transcription of the polymerase gene may not be a strand-break-dependent process. The noninducibility of the polymerase gene following DNA damage suggested that there may be adequate levels of the polymerase in the cells to cope with DNA damage. To test this hypothesis we examined the efficacy of DNA repair in Cos cells engineered to overexpress the polymerase. Although there was a slight augmentation of the repair rate, this increase was apparent only after very high levels of DNA damage and only at early repair times. After a longer repair period, the extent of repair in control cell was similar to that in the cell overexpressing the polymerase. We thus conclude that the basal levels of the polymerase are adequate for significant amounts of DNA damage.
Carcinogenesis 1990 Jan
PMID:Expression of the poly(ADP-ribose) polymerase gene following natural and induced DNA strand breakage and effect of hyperexpression on DNA repair. 210 80

Vitamin B6 is involved in many biological processes of potential relevance to carcinogenesis and tumor growth, including DNA synthesis and maintenance of immunocompetence, yet very little information exists on B6 nutritional status in childhood leukemia. Using a radioenzymatic assay, the authors measured plasma pyridoxal 5'-phosphate (PLP), the biologically active form of B6, in 11 newly diagnosed untreated children with leukemia and 11 age-matched controls. The children with leukemia had significantly lower PLP levels than the controls. In 26 additional leukemia patients and 26 additional controls, a high-performance liquid chromatography assay also demonstrated lower plasma PLP levels in childhood leukemia compared with controls. These differences were significant for both acute lymphoblastic leukemia (ALL) and for acute nonlymphoblastic leukemia (ANLL). The PLP values did not correlate with indices of leukemia cell burden, but did correlate with reported B6 intake, suggesting that illness-related diet changes are at least partially responsible for the low PLP levels. Before any chemotherapy, overall nutritional status was suboptimal in 53% of ALL cases and 57% of ANLL cases. Newly diagnosed children with leukemia have suboptimal overall nutrition as well as suboptimal vitamin B6 status.
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PMID:Abnormal vitamin B6 status in childhood leukemia. 224

Increased energy intake and physical inactivity have been shown to heighten the risk of breast, large bowel, and other cancers. Large body size and fatness, as measured by adult stature, body weight and body mass indices, are positively related to a variety of cancers, including breast, colorectum, prostate, endometrium, kidney, and ovary, as well as to total cancer incidence or mortality in many investigations, although conflicting reports exist. Adult weight gain has also been specifically implicated in a few etiologic studies of breast and large bowel cancer. Furthermore, increased birthweight and childhood stature have been linked to increased risk of leukemia, lymphoma, osteogenic sarcoma, and central nervous system malignancies between infancy and young adulthood. Greater body weight also adversely affects breast cancer survival. These findings are complementary and support a role for positive energy balance in promoting human carcinogenesis. Potential mechanisms are discussed.
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PMID:Energy balance, body size, and cancer. 225 89

Parental occupational exposures might affect childhood cancer in the offspring through genetic changes in the ovum or sperm or through transplacental carcinogenesis. The 24 published epidemiologic studies of this association have all used case-control designs, with controls generally selected from birth certificates or from general population sampling. Occupational exposures were inferred from job titles on birth certificates or through interviews. A large number of occupation-cancer associations have been reported, many of which were not addressed or not confirmed in other studies. Several associations have been found with consistency: paternal exposures in hydrocarbon-associated occupations, the petroleum and chemical industries, and especially paint exposures have been associated with brain cancer; paint exposures have also been linked to leukemias. Maternal exposures have received much less attention, but studies have yielded strongly suggestive results linking a variety of occupational exposures to leukemia and brain cancer. The primary limitations in this literature are the inaccuracy inherent in assigning exposure based on job title alone and imprecision due to limited study size. Although no etiologic associations have been firmly established by these studies, the public health concerns and suggestive data warrant continued research.
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PMID:Parental occupation and childhood cancer: review of epidemiologic studies. 227 30

A multi-step model of the carcinogenesis for adult T-cell leukemia-lymphoma (ATL) has been reviewed here according to the authors observations. Epidemiological studies demonstrated that in most japanese ATL cases the disease developed from those who acquired infection of the causal agent, human T-cell lymphotropic virus type 1 (HTLV-1), during early infancy, probably through breast-feeding. Therefore, the latency period between the acquisition of HTLV-1 and clinical manifestation of ATL can be represented by the age of disease onset. It has been demonstrated by us that the age distribution of ATL onset can be described by a single Weibull distribution function, which is considered to be a feasible mathematical model for multistep carcinogenesis. Based on the present model, it is assumed that age-dependent accumulation of nearly five leukemogenic events, most likely somatic mutations, within the target cell(s) might be required prior to the disease onset.
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PMID:[Multi-stop carcinogenesis model for adult T-cell leukemia]. 239 8

Procarbazine hydrochloride (PCZ), a chemotherapeutic agent used extensively to treat Hodgkins disease and other tumors, induces leukemia, lymphoma, mammary gland and other solid tumors in rodents and non-human primates and is strongly implicated as a leukemogen in humans. Lipotrope (choline and methionine) deficiency is a powerful potentiator of chemical carcinogenesis in liver and, under some conditions, in other tissues in rodents. Methotrexate (MTX), another commonly used chemotherapeutic agent, interferes with one-carbon metabolism and limits availability of lipotropes. Studies of PCZ carcinogenesis in lipotrope-deficient or MTX-treated male rats are reported, showing that both deficiency and MTX increased PCZ carcinogenicity in the mammary gland. In addition, PCZ was found to induce abnormalities of hepatic choline metabolism. Weanling male Sprague-Dawley rats were fed control (C) or lipotrope-deficient (D) diet. After 3 weeks, C and D rats were given PCZ, MTX, the two drugs together or 0.9% saline by i.p. injection. Doses were 0.2 or 0.5 mg MTX/kg or 25 mg PCZ/kg, given 2 or 3 days per week for 5 or 14 weeks. After 5 weeks of drug treatment livers were assayed for choline, phosphatidylcholine, phosphocholine (PCho), glycerophosphocholine and betaine. PCZ perturbed choline metabolism, increasing hepatic choline and PCho in deficient or MTX-treated rats and, to a smaller extent, in rats fed control diet. MTX markedly enhanced the effect of PCZ on choline metabolism. PCZ-induced mammary tumor incidence was increased 50-70% by lipotrope deficiency or by MTX. In PCZ-treated rats, cumulative probability of bearing a mammary tumor was significantly increased by lipotrope deficiency (P = 0.05), and was increased similarly but not significantly by MTX (P = 0.1). Cumulative tumor numbers per group in PCZ-treated rats were significantly greater in both deficient and MTX-treated rats compared to rats fed control diet (P less than 0.005). Incidences of leukemia, lymphoma and Zymbal's gland tumors induced by PCZ were not significantly altered by diet or MTX.
Carcinogenesis 1990 Sep
PMID:Procarbazine carcinogenicity in methotrexate-treated or lipotrope-deficient male rats. 240 Oct 40

Normal rat kidney cells, infected with Moloney murine leukemia virus, were treated with 3-methylcholanthrene at passage 5 postinfection. Foci of transformed cells appeared after 9-11 passages following this treatment. Characterization of four different randomly isolated foci revealed a striking diversity with respect to various tested phenotypic parameters. Remarkable differences were observed among these transformed clones regarding their cell morphology, growth rate, saturation density, serum requirements, virus release and its response to rat and mouse fibroblast interferons. This study demonstrates that cell transformation by chemical-retroviral co-carcinogenesis may lead to the formation of phenotypically heterogeneous tumor cells.
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PMID:Phenotypic heterogeneity in 3-methylcholanthrene-induced transformation of normal rat kidney cells infected with Moloney murine leukemia virus. 241 82


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