Specificity and inducibility of the metabolic reduction of chromium(VI) mutagenicity by subcellular fractions of rat tissues.

The mutagenicity of sodium dichromate in the Ames test was decreased as a consequence of chromium(VI) reduction by tissue postmitochondrial (S-9 or S-12) fractions from untreated rats with the following rank of efficiency: liver; kidney; and lung. The effects of lung preparations were significantly enhanced following the intratracheal administration of high doses (0.25 mg/kg) of dichromate itself, 5 times per week for 4 weeks (i.e., 20 fractionated instillations). No changes were conversely detected following single weekly doses of 1.25 mg/kg for the same period (i.e., four cumulative instillations). The local stimulation of chromium(VI) metabolism was also confirmed by testing the mutagenicity of calcium chromate and chromium trioxide, whereas the metabolism of a number of other activatable or deactivatable mutagens was not significantly affected by intratracheal treatment with chromium(VI). Of three enzyme inducers injected i.p. which modified the spectral properties and/or concentration of cytochromes P-450 in liver and lung microsomes, only Aroclor 1254 proved to stimulate chromium(VI) metabolism in lung cells. In liver cells, Aroclor 1254 and to a lower extent phenobarbital induced chromium(VI) reduction, while 3-methylcholanthrene was ineffective. Pretreatment of rats with these three compounds resulted in a selective induction of the metabolic activation of promutagens [benzo(a)pyrene and its trans-7,8-diol, 2-aminofluorene, aflatoxin B1] and of the metabolic deactivation of direct-acting mutagens [2-methoxy-6-chloro-9-[3-(2-chloroethyl)-aminopropylamino] acridine X 2HCl, epichlorohydrin, 4-nitroquinolino-N-oxide] by S-12 and microsomal fractions. These findings indicate that, in addition to already recognized detoxification mechanisms operating outside target cells (26), specific and inducible chromium-reducing pathways, mediating threshold phenomena in chromium carcinogenesis, do also occur in the intracellular environment.

[1]  L. R. White,et al.  Response of a human tumour cell line to chronic potassium dichromate exposure. , 1981, Toxicology.

[2]  S. Flora.  Metabolic deactivation of mutagens in the Salmonella-microsome test , 1978, Nature.

[3]  B. Ames,et al.  Revised methods for the Salmonella mutagenicity test. , 1983, Mutation research.

[4]  A. Levis,et al.  Mutagenic and cytogenetic effects of chromium compounds , 1982 .

[5]  S. De Flora,et al.  Interpretations on chromium mutagenicity and carcinogenicity. , 1983, Progress in clinical and biological research.

[6]  S. Gray,et al.  The tagging of red cells and plasma proteins with radioactive chromium. , 1950, The Journal of clinical investigation.

[7]  K. Jennette,et al.  Electron-transport cytochrome P-450 system is involved in the microsomal metabolism of the carcinogen chromate. , 1981, Journal of inorganic biochemistry.

[8]  S. Flora,et al.  Metabolic activation and deactivation of mutagens by preparations of human lung parenchyma and bronchial tree. , 1984, Mutation research.

[9]  S. De Flora,et al.  High sensitivity of Salmonella TA102 in detecting hexavalent chromium mutagenicity and its reversal by liver and lung preparations. , 1983, Mutation research.

[10]  D. Jenssen,et al.  Mutagenicity of fume particles from stainless steel welding. , 1977, Scandinavian journal of work, environment & health.

[11]  S. De Flora,et al.  Oxidation of inactive trivalent chromium to the mutagenic hexavalent form. , 1978, Mutation research.

[12]  S. Flora.  Study of 106 organic and inorganic compounds in the Salmonella /microsome test , 1981 .

[13]  K. Jennette.  Microsomal reduction of the carcinogen chromate produces chromium(V) , 1982 .

[14]  C. Sanderson.  The uptake and retention of chromium by cells. , 1976, Transplantation.

[15]  B. Ames,et al.  A new Salmonella tester strain (TA102) with A X T base pairs at the site of mutation detects oxidative mutagens. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[16]  S. De Flora,et al.  Metabolic deactivation of hexavalent chromium mutagenicity. , 1978, Mutation research.

[17]  S. De Flora,et al.  Prominent role of DT-diaphorase as a cellular mechanism reducing chromium(VI) and reverting its mutagenicity. , 1985, Cancer research.

[18]  S. Langård.  Absorption, transport and excretion of chromium in man and animals , 1982 .

[19]  S. Orrenius,et al.  Isolation and comparison of endoplasmic reticulum membranes and their mixed function oxidase activities from mammalian extrahepatic tissues. , 1979, Pharmacology & therapeutics.

[20]  D. Bickers,et al.  Polychlorinated biphenyls: a new type of inducer of cytochrome P-448 in the liver. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[21]  H. Weber.  Long-term study of the distribution of soluble chromate-51 in the rat after a single intratracheal administration. , 1983, Journal of toxicology and environmental health.

[22]  M. Plummer,et al.  International agency for research on cancer. , 2020, Archives of pathology.

[23]  J. Depierre,et al.  Measurement of cytochrome P-450 in the presence of large amounts of contaminating hemoglobin and methemoglobin. , 1978, Analytical biochemistry.

[24]  T. Omura,et al.  THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. I. EVIDENCE FOR ITS HEMOPROTEIN NATURE. , 1964, The Journal of biological chemistry.

[25]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.