methyldimethylaminoazobenzene

Summary

Summary: A very potent liver carcinogen.

Top Publications

  1. Ringer D, Panzeter P, DeCicco L. Alterations in epidermal growth factor binding to hepatic membranes following dietary exposure of rats to known hepatocarcinogens. Toxicol Lett. 1997;91:7-12 pubmed
    ..These findings show that decreases in EGF binding capacity are caused by a diverse group of known hepatocarcinogenic compounds at an early stage in the carcinogenesis process...
  2. Nakajima T, Ichikawa S, Uchida S, Komada T. Effects of a protein-bound polysaccharide from a basidiomycetes against hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene in rats. Clin Ther. 1990;12:385-92 pubmed
    ..The results indicate that PSK had a suppressive effect on 3-MDAB-induced hepatocarcinogenesis...
  3. Yamamoto R, Tatsuta M, Yamamoto T, Terada N. The later administration of progesterone more rapidly activates dormant mouse mammary tumor cells initiated by 3'-methyl-4-dimethylaminoazobenzene. Cancer Lett. 1996;100:41-5 pubmed
  4. Ohkawa K, Abe T, Hatano T, Takizawa N, Yamada K, Takada K. The facilitated effect of retinol on rat hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene. Carcinogenesis. 1991;12:2357-60 pubmed
    ..These results indicated that the administration of retinol in the early stages of hepatocarcinogenesis enhanced the tumor induction, possibly due to the fixation of malignant transformation of the cells...
  5. Winton D, Flaks B, Flaks A. Quantitative electron microscopy of carcinogen-induced alterations in hepatocyte rough endoplasmic reticulum. I. Chronic effect of 3'MeDAB and short-term effects of azo dyes of different carcinogenic potentials. Carcinogenesis. 1988;9:987-99 pubmed
    ..At least with the azo dyes used in this study, the extent of rough ER disaggregation appears to be related to hepatocarcinogenesis...
  6. Scoazec J, Moreau A, Maurice M, Hassan N, Feldmann G. Detection of a biliary cell membrane glycoprotein in the serum of cholangiocarcinoma-bearing rats. Possible relevance to the membrane proteins used as serum tumor markers in humans. Lab Invest. 1990;62:459-66 pubmed
    ..A comparable mechanism is likely to explain how certain membrane glycoproteins used as serum markers in human malignancy may reach the blood...
  7. Hammad H, Higashi T, Tateishi N, Hanatani M, Sakamoto Y. Lipid peroxidation in the liver of carcinogen-resistant rats. Biochim Biophys Acta. 1990;1045:99-106 pubmed
    ..The higher ADH activity may explain the decreased lipid peroxidation in R rats at least partly, if this enzyme is involved in lipid peroxidation...
  8. Sarkar A, Mukherjee B, Chatterjee M. Inhibition of 3'-methyl-4-dimethylaminoazobenzene-induced hepatocarcinogenesis in rat by dietary beta-carotene: changes in hepatic anti-oxidant defense enzyme levels. Int J Cancer. 1995;61:799-805 pubmed
    ..Our results confirm that BC is protective in limiting the action of 3'-Met-DAB during the initiation phase of hepatocarcinogenesis...
  9. Nishikawa S. [Biochemical and immunohistochemical studies on alteration of aldolase isozymes in rat liver in the process of hepatocarcinogenesis by administration of a diet containing 3'-methyl-4-dimethylaminoazobenzene]. Hokkaido Igaku Zasshi. 1989;64:440-9 pubmed
    ..Serum aldolase A levels were not significantly elevated in rats with liver cancer in comparison to rats with non-cancer...

More Information

Publications62

  1. Todaka N, Higashi K, Yan Y, Abe T, Yamashiro K, Hiai H. Investigation of possible involvement of several genes related to development of hepatocarcinogenesis in rats. J UOEH. 2000;22:119-32 pubmed
    ..A reduced induction of AFP mRNA was observed in DRH rats under the same conditions. Further study will be needed to explain the lower tumor susceptibility in the DRH rat...
  2. Kuroda K, Terao K, Akao M. Inhibitory effect of fumaric acid on hepatocarcinogenesis by thioacetamide in rats. J Natl Cancer Inst. 1987;79:1047-51 pubmed
    ..The inhibitory effect of FA on TAA carcinogenesis was so marked that no hepatic carcinomas were found in both groups fed FA in combination with TAA...
  3. Shimpo K, Takahashi H, Tsuda H, Hibino T, Kawai K, Kimura C, et al. Inhibition of hepatocellular carcinoma development and erythrocyte polyamine levels in ODS rats fed on 3'-methyl-4-dimethylaminoazobenzene by hemicalcium ascorbate, 2-O-octadecylascorbic acid, and ascorbyl palmitate. Cancer Detect Prev. 1996;20:137-45 pubmed
    ..We have also studied the correlation of erythrocyte (RBC) polyamine levels and HCC development. RBC polyamine levels were inhibited by Ca-Asc and its derivatives, indicating it may be a marker of hepatocarcinogenesis...
  4. Ishii K, Karube H, Fujita Y, Shibata H, Okudaira M, Tsuchiya M. Is macronodular liver cirrhosis an irreversible lesion? Changes in the intrahepatic micro-vasculature treated with estradiol benzoate in rats. Angiology. 1990;41:512-7 pubmed
    ..It is concluded that EB provides a salutary effect on the intrahepatic microcirculatory system, by means of which MNLC can be shown to be a reversible lesion...
  5. Iwai M, Kashiwadani M, Kitagawa Y, Kashima K, Ibata Y, Yasuda K. Immunocytochemical investigation of rat gamma-glutamyl transpeptidase in chemically-induced hepatocarcinogenesis using monoclonal antibody. Arch Histol Cytol. 1994;57:119-27 pubmed
    ..In livers with developing hepatocellular carcinomas, the immunoreactivity was present on the membranes of irregularly dilated bile canaliculi in malignant cells...
  6. Ando N, Shimizu M, Okuno M, Matsushima Nishiwaki R, Tsurumi H, Tanaka T, et al. Expression of retinoid X receptor alpha is decreased in 3'-methyl-4-dimethylaminoazobenzene-induced hepatocellular carcinoma in rats. Oncol Rep. 2007;18:879-84 pubmed
  7. Merkulova T, Kropachev K, Timofeeva O, Vasiliev G, Levashova Z, Ilnitskaya S, et al. Species-specific effects of the hepatocarcinogens 3'-methyl-4-dimethyl-aminoazobenzene and ortho-aminoazotoluene in mouse and rat liver. Mol Carcinog. 2005;44:223-32 pubmed
    ..32-0.47 g/mL interval of ammonium sulfate concentration. In contrast, non-specific hepatocarcinogen DENA was effective upon being added directly to Fraction I, implying a different mechanism of its action...
  8. Tsuda H, Asamoto M, Ogiso T, Inoue T, Ito N, Nagao M. Dose-dependent induction of liver and thyroid neoplastic lesions by short-term administration of 2-amino-3-methylimidazo[4,5-f]quinoline combined with partial hepatectomy followed by phenobarbital or low dose 3'-methyl-4-dimethylaminoazobenzene promo. Jpn J Cancer Res. 1988;79:691-7 pubmed
    ..The development of thyroid tumors initiated by the IQ treatment was significantly enhanced by the administration of PB, whereas Zymbal gland tumors induced by IQ did not show any correlation with either PB or 3'-Me-DAB treatment...
  9. Saito S, Hashimoto N, Tokita K, Toyoda M, Suzuki Y, Goldstein B, et al. Changes of expressions of phosphotyrosine phosphatases in rat hepatocellular carcinoma induced by 3'-methyl-4-dimethylamino-azobenzene. Biochem Biophys Res Commun. 1996;227:406-12 pubmed
    ..This increase of expression of SHPTP2 may contribute to the progression of hepatocellular carcinoma in this rat model...
  10. Ogoshi K, Yanagi S, Moriyama T, Arachi H. Accumulation of aluminum in cancers of the liver, stomach, duodenum and mammary glands of rats. J Trace Elem Electrolytes Health Dis. 1994;8:27-31 pubmed
    ..The present study demonstrated that aluminum accumulated in experimentally induced carcinomas in rats, i.e., cancers of the liver, stomach, duodenum and mammary glands...
  11. Hirano T, Sakai A, Ootsuyama Y, Kasai H. Chronic alcohol consumption prevents 8-hydroxyguanine accumulation in 3'-methyl-4-dimethylaminoazobenzene-treated mouse liver. Biochem Biophys Res Commun. 2009;387:316-20 pubmed publisher
    ..These findings suggested that 12% ethanol consumption may reduce the risk of 3'-MeDAB-induced carcinogenesis by decreasing 8-OH-Gua accumulation...
  12. Scoazec J, Maurice M, Moreau A, Feldmann G. Analysis of hepatocyte plasma membrane polarity during rat azo dye hepatocarcinogenesis using monoclonal antibodies directed against domain-associated antigens. Cancer Res. 1988;48:6882-90 pubmed
    ..techniques that changes in hepatocyte plasma membrane polarity occur at every stage of 3'-methyldimethylaminoazobenzene-induced hepatocarcinogenesis...
  13. Lorenzini E, Buccellato F, Scalabrino G. Different patterns of expression of ornithine decarboxylase mRNAs in rat liver after acute administration of hepatocarcinogens. Carcinogenesis. 1996;17:1323-9 pubmed
    ..7 kb) in rat liver seems to be expressed not only constitutively but is also inducible...
  14. Sakagami H, Takeda M, Utsumi A, Fujinaga S, Tsunoda A, Yasuda N, et al. Effect of sodium benzylideneascorbate on chemically-induced tumors in rats. Anticancer Res. 1993;13:65-71 pubmed
    ..These data suggest that the conditions of SBA administration should be re-established for each tumor sample to produce maximum antitumor activity...
  15. Srinivasan K, Bhargava M. Hepatic binding proteins translocating azo dye carcinogen metabolites from cytoplasm into nucleus in rats. Food Chem Toxicol. 2004;42:503-8 pubmed
    ..This suggests that the interaction of azo dye metabolites with nuclear macromolecules necessitate further prior processing which actually may occur in the nucleus...
  16. Liu H, Higashi K, Hiai H. Role of resistant Drh1 locus in chemical carcinogen-induced hepatocarcinogenesis in rats: analysis with a speed congenic strain. Cancer Sci. 2005;96:164-9 pubmed
    ..The major role of Drh1 is effective removal of the hepatocytes newly recruited to proliferate after chemical injury. Resistance to preneoplastic lesions in DRH rats may well be based on similar mechanism...
  17. Lertprasertsuke N, Shinoda M, Takekoshi S, Tsutsumi Y, Yamamoto Y, Niki E, et al. Different effects of carbon tetrachloride on carcinogen-induced hepatocellular carcinoma and normal liver of the rat: lowered lipid peroxidation and accelerated necrosis in cancer. Jpn J Cancer Res. 1991;82:503-10 pubmed
    ..Peroxidation of PUFAs might act as a "shock absorber" against free radical-induced toxic cell death in normal cells...
  18. Karaki Y, Munakata S, Saeki T, Hirota S, Fujimaki M. Appearance of a carcinoid-like pattern in rat hepatic tumors induced by 3'-methyl-4-dimethyl-aminoazobenzene. Jpn J Cancer Res. 1991;82:397-402 pubmed
    ..These results suggest that 3'-MeDAB might induce hepatic carcinoid under certain conditions, though we have yet to confirm the development of a pure hepatic carcinoid due to this substance...
  19. Lertprasertsuke N, Shinoda M, Takekoshi S, Yoshimura S, Watanabe K. Suppression of messenger ribonucleic acid for glutathione peroxidase in chemically induced rat hepatocellular carcinoma and its biological significance. Tokai J Exp Clin Med. 1990;15:285-92 pubmed
    ..It was suggested that suppressed expression of GSH-PO in carcinogen-induced hepatocellular carcinomas occurred at the level of mRNA transcription...
  20. Yamamoto R, Iishi H, Tatsuta M, Tsuji M, Terada N. Suppressive effect of estrogen on hepatocellular tumorigenesis induced in mice by 3'-methyl-4-dimethylaminoazobenzene. Exp Toxicol Pathol. 1993;45:325-8 pubmed
    ..The present results suggest that the ovarian hormone, estrogen suppresses the development of hepatocellular tumors induced by 3'-Me-DAB, exerting its effect from about 6 months of age...
  21. Hirano T, Higashi K, Sakai A, Tsurudome Y, Ootsuyama Y, Kido R, et al. Analyses of oxidative DNA damage and its repair activity in the livers of 3'-methyl-4-dimethylaminoazobenzene-treated rodents. Jpn J Cancer Res. 2000;91:681-5 pubmed
    ..6-fold and 1.6-fold, respectively. These experiments suggest that 3'-MeDAB increases 8-OH-Gua generation in rodent liver DNA and the 8-OH-Gua repair assay is a reliable marker of cellular oxidative stress induced by carcinogens...
  22. Denda A, Kitayama W, Konishi Y, Yan Y, Fukamachi Y, Miura M, et al. Genetic properties for the suppression of development of putative preneoplastic glutathione S-transferase placental form-positive foci in the liver of carcinogen-resistant DRH strain rats. Cancer Lett. 1999;140:59-67 pubmed
    ..The intrinsic properties observed in this study may be related, at least in part, to the low incidence of liver tumors induced by hepatocarcinogens in DRH rats...
  23. Sakamoto S, Hirai H, Taga H, Uchikoshi T, Sunaga T, Endo Y, et al. Thymidine kinase and alpha-fetoprotein as biochemical markers of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene treatment in rats. Carcinogenesis. 1990;11:145-50 pubmed
    ..These results indicate that early biochemical changes in 3'-MeDAB-induced hepatocarcinoma in rats may serve as a useful model and provide a valuable insight in hepatocarcinogensis...
  24. Fu Y, Deng W, Li Y, Sugiyama T. [Quantitative analysis of p53 and related genes mRNA in rat hepatocarcinogenesis induced by 3'-Me-DAB]. Ai Zheng. 2003;22:35-41 pubmed
  25. Kelley F, Kopac C, Rosselli J. Advanced health assessment in nurse practitioner programs: follow-up study. J Prof Nurs. 2007;23:137-43 pubmed
    ..There was an emergence of more creative strategies: the use of standardized patients, online coursework, videotaping, "live" patients, and simulations...
  26. Bryzgalov L, Ershov N, Ilnitskaya S. FOXA transcription factors determine the amplitude of glucocorticoid induction of tyrosine aminotransferase in mice. Bull Exp Biol Med. 2007;144:722-4 pubmed
    ..Our results suggest that FOXA proteins determine glucocorticoid induction of tyrosine aminotransferase in mice (similarly to rats)...
  27. Mori Y, Niwa T, Hori T, Toyoshi K. Mutagenicity of 3'-methyl-N,N-dimethyl-4-amino azobenzene metabolites and related compounds. Carcinogenesis. 1980;1:121-7 pubmed
  28. Sakamoto S, Hirai H, Taga H, Uchikoshi T, Sunaga T, Endo Y, et al. Inhibition by 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil of hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene in rats. Anticancer Res. 1991;11:561-6 pubmed
    ..These results indicate that the suppression of de novo synthesis in pyrimidine metabolism prevents hepatocarcinogenesis...
  29. Kim Y, Paik E, Lee M, Kim K, Chai K, Ahn Y. A study on the regulation of translocation of glucose transporters during hepatocarcinogenesis induced by 3'-Me DAB. Yonsei Med J. 1990;31:315-24 pubmed
    ..These results indicate that increased glucose transport seems to be more likely due to reciprocal redistribution of GTs between plasma membrane and LDM fractions...
  30. Miyazaki M, Wahid S, Sato J. In vivo and in vitro test for growth potential of liver cells from rats during early stage of hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene. J Cancer Res Clin Oncol. 1989;115:1-8 pubmed
    ..As described above, liver cells from rats fed 3'-Me-DAB demonstrated much greater proliferative ability than normal control cells in vivo and in vitro...
  31. Carr B. Pleiotropic drug resistance in hepatocytes induced by carcinogens administered to rats. Cancer Res. 1987;47:5577-83 pubmed
  32. Miyamoto K, Wakusawa S, Nomura M, Sanae F, Sakai R, Sudo K, et al. Effects of gomisin A on hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene in rats. Jpn J Pharmacol. 1991;57:71-7 pubmed
    ..Thus, phenobarbital acted as a promoter of cells initiated by 3'-MeDAB; on the other hand, gomisin A showed a weak suppressive effect on tumor promotion...
  33. Hirai H, Taga H, Endo Y, Iino S, Sugiura M, Futagawa S. [The effect of a mixture of tegafur with uracil (UFT) on hepatocarcinogenesis in rats induced by 3'-methyl-4-dimethylaminoazobenzene. I. The influence on production of alpha-fetoprotein]. Gan To Kagaku Ryoho. 1988;15:101-8 pubmed
    ..These results show that if the administration of UFT was commenced at the same time with feeding 3'-MeDAB diet, the hepatocarcinogenesis and AFP production are strongly inhibited...
  34. Nakamatsu K, Nishimura Y, Suzuki M, Kanamori S, Maenishi O, Yasuda Y. Erythropoietin/erythropoietin-receptor system as an angiogenic factor in chemically induced murine hepatic tumors. Int J Clin Oncol. 2004;9:184-8 pubmed
    ..To clarify the role of erythropoietin (Epo) in hepatic tumor angiogenesis, expression of Epo and its receptor (Epo-R) and content of Epo were investigated in murine chemically induced hepatic tumors...
  35. Kohnoe S, Maehara Y, Endo H. Difference in gene expression between azo-dye-induced primary hepatomas and corresponding transplantable ascites hepatoma lines in rats. Oncology. 1988;45:51-6 pubmed
    ..Southern blot analyses of the genomic DNAs showed that the different expressions might have occurred, with no major alteration in the gene structure...
  36. Liu H, Nobumoto K, Yamada Y, Higashi K, Hiai H. Modulation of genetic resistance to hepatocarcinogenesis in DRH rats by partial hepatectomy. Cancer Lett. 2003;196:13-6 pubmed
    ..In contrast, the F1 rats without PH rarely developed cancers. Such modulation was not due to the loss of the resistance allele, since none of 18 hepatocellular carcinomas in PH-F1 rats showed allelic imbalance at Drhl and Drh2...
  37. Yeoh G, Porter I, Arcus M, Douglas A. Transformation of cultured fetal rat liver cells by MDAB and phenobarbital. Morphological, biochemical and immunocytochemical characterization of cell lines. Carcinogenesis. 1989;10:1015-27 pubmed
    ..It can be concluded from these studies that it is possible to transform cells derived from fetal rat liver in culture using a hepatocarcinogen.(ABSTRACT TRUNCATED AT 400 WORDS)..
  38. Yan Y, Zeng Z, Higashi S, Denda A, Konishi Y, Onishi S, et al. Resistance of DRH strain rats to chemical carcinogenesis of liver: genetic analysis of later progression stage. Carcinogenesis. 2002;23:189-96 pubmed
    ..The GST-P induction is differentially controlled by stages of hepatocarcinogenesis and the DRH resistance to carcinogenesis is principally attributed to the QTLs on RNO4 out of two resistance QTLs identified in the pre-neoplastic stage...
  39. Adamson R. Induction of hepatocellular carcinoma in nonhuman primates by chemical carcinogens. Cancer Detect Prev. 1989;14:215-9 pubmed
    ..One nitrosamine, diethylnitrosamine, is a predictable and potent inducer of HCC and is useful for establishment of a nonhuman primate model for numerous oncologic studies...
  40. Coles B, Beale D, Miller D, Lay J, Kadlubar F, Aitken A, et al. The binding of an aminoazo dye carcinogen to a specific methionine residue in rat liver alcohol dehydrogenase in vivo. Chem Biol Interact. 1987;64:181-92 pubmed
    ..This highly specific reaction of the carcinogen with alcohol dehydrogenase may be regarded as a major detoxication reaction...
  41. Miyagi T, Koseki M, Tsuiki S. Comparative study of the levels of sialyltransferases responsible for the formation of sugar chains in glycoproteins and gangliosides in rat liver and hepatomas. Jpn J Cancer Res. 1988;79:742-9 pubmed
    ..When compared with Wistar liver, MeDAB-induced hepatoma was higher in lactosylceramide- and lower in GM3-sialyltransferase activity, but these two activities were both lower in AH-109A compared with Donryu liver...
  42. Winton D, Flaks B. Effect of fasting on aggregation of hepatocyte rough endoplasmic reticulum in adrenalectomized and 3'MeDAB-treated rats: quantitative electron microscope study. Br J Exp Pathol. 1988;69:877-89 pubmed
    ..The implications of this are discussed in terms of known interrelations between glucocorticoids and chemical carcinogenesis in the rat liver...
  43. Dong J, Kilianska Z, Fukuda K, Chiu J. The appearance of hepatoma-associated chromosomal non-histone proteins in rat liver after a single dose of 3'-MDAB followed by treatment of phenobarbital. Cancer Lett. 1990;51:259-67 pubmed
    ..The results of these studies demonstrate that the hepatoma-associated non-histone proteins are expressed not only in hepatoma cells, but also in hepatocyte cells committed to carcinogenesis...
  44. Nomura M, Nakachiyama M, Hida T, Ohtaki Y, Sudo K, Aizawa T, et al. Gomisin A, a lignan component of Schizandora fruits, inhibits development of preneoplastic lesions in rat liver by 3'-methyl-4-dimethylamino-azobenzene. Cancer Lett. 1994;76:11-8 pubmed
    ..This study suggests that gomisin A is a candidate for a chemopreventive drug inhibiting the promotion process in hepatocarcinogenesis...
  45. Chai K, Kim J, Lee H. Expressions of c-fos and c-myc genes during 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB)-induced rat hepatocarcinoma. Yonsei Med J. 1992;33:240-8 pubmed
  46. Li H, Lee G, Liu J, Nomura K, Ohtake K, Kitagawa T. Low frequency of ras activation in 2-acetylaminofluorene- and 3'-methyl-4-(dimethylamino)azobenzene-induced rat hepatocellular carcinomas. Cancer Lett. 1991;56:17-24 pubmed
  47. Winton D, Flaks B. Quantitative electron microscopy of carcinogen-induced alterations in hepatocyte rough endoplasmic reticulum. II. Modulation of the effects of 3'MeDAB by adrenalectomy and adrenal corticosteroids. Br J Exp Pathol. 1989;70:369-84 pubmed
    ..In the rat hepatocyte, rough ER stacking or aggregation appears to be at least partially under hormonal control...
  48. Sakamoto S, Taga H, Uchikoshi T, Kudo H, Suzuki S, Sugiura Y, et al. Synergistic effect of oral UFT in combination with cisplatin on DNA synthesis in rat hepatocarcinomas. Anticancer Res. 1993;13:631-4 pubmed
    ..e., UFT and CDDP showed a potent synergism on DNA synthesis in hepatocarcinomas...
  49. Yanagi S, Yamashita M, Hiasa Y, Kamiya T. Effect of ethanol on hepatocarcinogenesis initiated in rats with 3'-methyl-4-dimethylaminoazobenzene in the absence of liver injuries. Int J Cancer. 1989;44:681-4 pubmed
    ..Ethanol thus does not appear to enhance hepatocarcinogenesis, at least in the absence of liver injury...
  50. Terayama H, Shimizu N, Fukuzumi R. Calciferin and cathepsin D-like acid protease in serum in acute and chronic liver injuries in rats and humans. Clin Chem. 1989;35:2202-6 pubmed
    ..Later (13 weeks or more; chronic phase), however, only acid protease appeared to return to normal values...
  51. Yamamoto R, Tatsuta M, Terada N. Suppression by oestrogen of hepatocellular tumourigenesis induced in mice by 3'-methyl-4-dimethylaminoazobenzene. Br J Cancer. 1993;68:303-7 pubmed
    ..The present results suggest that E2 suppresses the development of adenomatous nodules and G-6-Pase deficient foci induced in the mouse liver by 3'-Me-DAB by actions on tissues other than the liver...
  52. Tamura S, Suzuki Y, Kikuchi K, Hatayama I, Sato K, Hirai R, et al. Tyrosine protein kinase in preneoplastic and neoplastic rat liver. Arch Biochem Biophys. 1988;265:373-80 pubmed
    ..Whether the liver and hepatoma kinases differ merely quantitatively or whether they differ even qualitatively, however, remains to be elucidated...
  53. Yamamoto N, Nomura K, Kayano T, Kitagawa T. Carcinogen daily dose-dependence of the biological features and development rate of hepatocellular carcinomas induced by 3'-methyl-4-dimethylaminoazobenzene in the rat. Cancer Lett. 1994;83:59-68 pubmed
    ..Thus the experimental results clearly document that biological features of neoplasms, viewed as a spectrum, may markedly differ according to the daily dose of the carcinogen applied...