Skip to main content
Log in

Alterations in dimethylnitrosamine-induced lethality and acute hepatotoxicity in rats during dietary thiamin, riboflavin and pyridoxine deficiencies

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Summary

The effects of dietary thiamin, riboflavin and pyridoxine deficienies on dimethylnitrosamine-induced lethality and hepatotoxicity were investigated in the rat. Development of deficienies was monitored by growth rate, food intake, ratio of liver weight to body weight and the biochemical parameters (thiamin diphosphate effects for thiamin deficiency, glutathione reductase activity coefficient for riboflavin deficiency and erythrocyte glutamate-oxaloacetate transaminase activity for pyridoxine deficiency). Thiamin deficiency slightly increased the acute toxicity of dimethylnitrosamine as observed by the lowering of the LD50 dose and the greater increase in the serum glutamate-oxaloacetate transaminase and serum glutamate-pyruvate transaminase levels. Riboflavin deficiency, on the other hand, slightly increased the LD50 dose of dimethylnitrosamine and resulted in less dimethylnitrosamine-induced damage to the liver. Pyridoxine deficiency did not affect the lethal dose nor significantly alter the transaminases levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

GOT:

glutamate-oxaloacetate transaminase

LD50 :

mean lethal dose

GPT:

glutamate-pyruvate transaminase

TPP:

thiamin-diphosphate

References

  • Brin M, Tai M, Ostashever AS, Kalinksky H (1960) The effect of thiamin deficiency on the activity of erythrocyte hemolysate transketolase. J Nutr 71:273–281

    Google Scholar 

  • Changbumrung S, Schelp FP, Hongtong K, Buavatana T, Supawan V, Migasena P (1985) Pyridoxine status in preschool children in northeast Thailand: a community survey. Am J Clin Nutr 41:770–775

    Google Scholar 

  • Dashman T, Kamm JJ (1979) Effects of high doses of vitamin E on dimethylnitrosamine hepatotoxicity and drug metabolism in the rat. Biochem Pharmacol 28:1485–1490

    Google Scholar 

  • Glatzle D, Weber F, Weiss O (1968) Enzymatic test for detection of a riboflavin deficiency NADPH-dependent glutathione reductase of red blood cells and its action by FAD in vitro. Experientia 24:1122

    Google Scholar 

  • Heller S, Salkeld RM, Korner WF (1973) Vitamin B6 status in pregnancy. Am J Clin Nutr 26:1339–1348

    Google Scholar 

  • Litchfield JT, Wilcoxon F (1949) A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther 96:99–118

    Google Scholar 

  • Maduagwu EN, Frei E, Frank N, Spiegelhalder B, Preussmann R (1983) Nitrosamine metabolism in kwashiorkor rats. Biochem Pharmacol 32:3577–3581

    Google Scholar 

  • Magee PN, Barnes JM (1967) Carcinogenic nitroso compounds. Adv Cancer Res 10:163–246

    Google Scholar 

  • Reitman S, Frankel S (1957) A colorimetric method the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–63

    Google Scholar 

  • Ruchirawat M, Shank RC (1978) Oxidative metabolism of dimethylnitrosamine: correlation with toxicity. J Toxicol Environ Health 4:161–172

    Google Scholar 

  • Ruchirawat M, Saengchan S (1984) Effects of riboflavin on the dimethylnitrosamine demethylase system in the rat liver. J Natl Cancer Inst 72:1167–1171

    Google Scholar 

  • Ruchirawat M, Mahathannatrakul W, Sinrashatanant Y, Kittikool D (1978) Effect of thiamin deficiency on the metabolism and acute toxicity of dimethylnitrosamine in the rat. Biochem Pharmacol 27:1783–1786

    Google Scholar 

  • Skaare JU, Nafstad I (1978) Interaction of vitamin E and selenium with the hepatotoxic agent dimethylnitrosamine. Acta Pharmacol Toxicol 43:119–128

    Google Scholar 

  • Swann PF, McLean AEM (1971) Cellular injury and carcinogenesis. The effect of a protein-free high carbohydrate diet on the metabolism of dimethylnitrosamine in the rat. Biochem J 124:283–288

    Google Scholar 

  • Swann PF, Kaufman DG, Magee PM, Mace R (1980) Induction of kidney tumors by a single dose of dimethylnitrosamine: dose response and influence of diet and benzo [a] pyrene pretreatment. Br J Cancer 41:285–294

    Google Scholar 

  • Ton CCT, Fong LYY (1984) The effects of ascorbic acid deficiency and excess on the metabolism and toxixity ofN-nitrosodimethylamine andN-nitrosodiethylamine in the guinea pig. Carcinogenesis 5:553–536

    Google Scholar 

  • Vimokesant SL, Hilker DM, Nakornchai S, Rungruangsak K, Dhanamitta S (1975) Effect of betal nut and fermented fish on the thiamin status of northestern Thai. Am J Clin Nutr 28:1458–1463

    Google Scholar 

  • Vudhivai N, Changbumrung S, Schelp FP, Vorasanta S, Prayurahong B, Migasena P (1986) Riboflavin status in preschool children in northeast Thailand: a community survey. J Med Assoc Thai 69:543–548

    Google Scholar 

  • Wang T, Miller KW, Tu YY, Yang CS (1985) Effects of riboflavin deficiency on metabolism of nitrosamines by rat liver microsome. J Natl Cancer Inst 74:1291–1297

    Google Scholar 

  • Wogan GN, Newberne PM (1967) Dose-response characteristics of aflatoxin B1carcinogenesis in the rat. Cancer Res. 27:2370–2376

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Dedicated to Professor Dr. D. Schmähl on the occasion of his 65th birthday

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ruchirawat, M., Navasumrit, P., Aramphongphan, A. et al. Alterations in dimethylnitrosamine-induced lethality and acute hepatotoxicity in rats during dietary thiamin, riboflavin and pyridoxine deficiencies. J Cancer Res Clin Oncol 116, 599–603 (1990). https://doi.org/10.1007/BF01637080

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01637080

Key words

Navigation