Abstract
One of the commonest reasons for a species difference in toxicity is a species difference in the route or rate of biotransformation of a chemical to its toxic metabolite. The biotransformation of foreign compounds usually occurs in two stages termed phase 1 and phase 2 reactions. The major phase 1 reactions include oxidation, reduction and hydrolysis, leading to the conversion of parent compound into substrate’s suitable for phase 2 conjugation reactions. The interplay between the two phases is important for the biotransformation of foreign compounds, particularly with regard to the balance between activation and detoxification.
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References
Alden C L, Kanerva R L, Ridder G and Stone L C (1984) The pathogenesis of the nephrotoxicity of volatile hydrocarbons in the male rat. In Renal effects of Petroleum Hydrocarbons. (MA Mehlman, GP Hemstreet, J J Thorpe and NK Weaver Eds) pp107–120, Princeton Publ N J.
Borghoff SJ, Miller AB, Bowen JP and Swenberg JA (1991) Characteristics of chemical binding to α2u-globulin in vitro-evaluating the structure- activity relationships.Toxicol Appl Pharmacol 107:228–238
Brady AM, Hasmall RL, Elcombe BM, Lock EA and DeMatteis F (1993) Effects of 2-[1 -(ethoxyimino)propyl]-3-hydroxy-5- (2,4,6- trimethylphenyl)cyclohex-2-eone on hepatic haem biosynthesis: species differences in hepatic porphyria Toxicology 84: 199–215
Chatterjee B, Demyan WF, Song CS, Garg BD and Roy AK (1989) Loss of androgenic induction of α2u-globulin gene family in the liver of NIH black rats. Endocrinology 125: 1385–1388
DeMatteis F, Gibbs AH and Holley AE (1987) Occurrence and biological properties of N-methylprotoporphyrin. Ann NY Acad Sci 514:30–40
DeMatteis F, Gibbs A H, Jackson A H and Weersinghe S (1980) Conversion of liver haem into N-substituted porphyrins or green pigments: nature of the substituent at the pyrrole nitrogen atom. Febs Lett 119:109- 112
Dietrich DR and Swenberg JA (1991) NCI-Black Reiter (NBR) male rats fail to develop renal disease following exposure to agents that induce α2u-globulin nephropathy. Fundam Appl Toxicol 16: 749–763
Frater Y, Brady AM, Lock EA and DeMatteis F (1993) Formation of N- methylprotoporphyrin in chemically induced protoporphyria. Arch Toxicol 67:179–185
Hard GC, Rodgers IS, Baetcke KP, Richards WL, McGaughy RE and Valcovic LR (1993) Hazard evaluation of chemicals that cause accumulation of α2u-globulin, hyaline droplet nephropathy, andtubule neoplasia in the kidneys of male rats. Environ Health Perspectives 99:313–349
Hodgson E and Guthrie FE (1980) Introduction to Biochemical Toxicology. Elsevier-North Holland
Lehmann-Mckeeman LD and Caudill D (1992a) Biochemical basis for mouse resistance to hyaline droplet neuropathy: lack of relevance of the α2u-globulin protein superfamily in this male rat-specific syndrome. Toxicol Appl Pharmacol 112: 214–221
Lehmann-McKeeman L D and Caudill D (1992b) α2u-globulin is the only member of the lipocalin protein superfamily that binds to hyaline droplets inducing agents. Toxicol Appl Pharmacol 116: 170–176
Lock EA (1993) α2u-globulin-related nephropathy. In Renal Disposition and Nephrotoxicity of Xenobiotics (MW Anders, W Dekant, D Henschler, H Oberleithner and S Silbernagl Eds) pp217–229 Academic Press London
Marks GS McCluskey SA, Mackie JE, Riddick DS and James CA (1988) Disruption of hepatic haem biosynthesis after interaction of xenobiotics with cytochrome P 450. Faseb 2 2774–2783
Oritz de Montellano, Beilan HS and Kunze KL (1981) N-methylprotoporphyrin IX: chemical synthesis and identification as the green pigment produced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine treatment. Proc Natl Acad Sci USA 78:1490–1494
Short BG, Burnett VL and Swenberg JA (1989) Elevated proliferation of proximal tubular cells and the localisation of accumulated α2u- globulin in F344 rats during chronic exposure to unleaded gasoline or 2,2,4-trimethylpentane.Toxicol Appl Pharmacol 101: 414–431
Swenberg JA, Short BG, Borghoff SJ, Strasser J and Charbonneau M (1989) The comparative pathobiologgy of α2u-globulin nephropathy. Toxicol Appl Pharmacol 97: 35–46
Timbrell JA (1991) Principles of Biochemical Toxicology 2nd Edition Taylor and Francis, London
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© 1995 Springer-Verlag Berlin Heidelberg
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Lock, E.A. (1995). Mechanisms Underlying Species-Specificity in Target Organ Toxicity. In: Degen, G.H., Seiler, J.P., Bentley, P. (eds) Toxicology in Transition. Archives of Toxicology, vol 17. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-79451-3_32
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DOI: https://doi.org/10.1007/978-3-642-79451-3_32
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