ACI

Inbr.F147 (NIH, 1989).

Colour: Agouti with white belly and feet.

Genet. A hⁱ.

Origin: Curtiss and Dunning 1926 at the Columbia University Institute for Cancer Research. To Heston 1945 at F30, to National Institutes of Health 1950 at F41. Subsequent sublines from Dunning or NIH.

Characteristics.

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Behaviour

Long latency to emerge into familar (11/12 male, 9/12 female) and novel environment (12/12 male, 11/12 female) (Harrington 1971a). Has a strong 24-hr. rhythm in wheel running activity when compared with LEW (Siebert and Wollnik 1991).

Biochemistry and physiology

Almost free of spike-wave discharges associate with absence epilepsy seen in strain WAG/Rij, while BN/Bi, B and G were intermediate (Inoue et al 1990). Low serum thyroxine (5/5) (Esber et al 1974). Low systolic blood pressure (17/17) (Hansen et al 1973). Low blood pressure (18/23), reaching 124_1.1 (SEM) mmHg at 10 weeks of age (Tanase et al 1982).

Copper deficiency results in pigment patterns similar to that of the mottled mouse, a model for Menkes' kinky hair syndrome (Miranda et al 1992). Liver gangliosides are of the a-type (cf LEA,LEW & BUF) (Kasai et al 1993)

Lifespan and spontaneous disease

Median survival 113 weeks in males, 108 weeks in females. Spontaneous tumours 46% testes,16% adrenal, 5% pituitary, 6% skin and ear duct and fewer of other types in males; 21% pituitary, 13% uterus, 11% mammary gland, 6% adrenal and fewer of other types in females. Other conditions include 28% of males and 20% of females with absent, hypoplastic or cystic kidneys on one side sometimes associated with an absent or defective uterine horn or atrophic testes on the same side (Maekawa and Odashima 1975). These abnormalities have a polygenic mode of inheritance (Cramer and Gill 1975). Spontaneous adenocarcinomas of ventral prostate seen in 7/41 untreated males at 34-37 months (Shain et al 1975, see also Ward et al 1980, Isaacs 1984). This is substantially increased by a high fat diet (Kondo et al 1994). High survival to 2 years of age at 74% (rank 2/5) in males and 70% (rank 1/5) in females. However, a high incidence of relatively mild chronic renal disease and a high incidence of hydronephrosis and the congenital renal agenesis may make the strain unsuitable for long-term toxicological studies (Solleveld and Boorman 1986). Four spontaneous kidney and five bladder tumours found among a cohort of 300 rats maintained for 30 months (Vanmoorsellar et al 1993).

Urolithiasis seen in 2/55 rats at an average age of 144 days (Kunstyr et al 1982). A diet deficient in choline and methionine has been used to develop a rat model of fatty liver transplantation (Teramoto et al 1993).

Drugs and chemicals

Many tumours induced by ptaquiloside, a carcinogen in the bracken fern (Hirono et al 1987). Caffein suppresses 2-acetylaminofluorine-induced hepatic tumours (Hosaka et al 1984). Effects of retinoids on tumours of the skin, prostate and endocrine pancreas studied by Ohshina et al (1985). Susceptible to the development of glioblastomas of a mixed oligo-astrocytic type following treatment with N-methyl-N-nitrosourea in the drinking water (Shibutani et al 1993). Like F344, refractory to the development of prostatic hyperplasia induced by citral compared with outbred Wistar and Sprague-Dawley rats (Scolnik et al 1994). Highly sensitive to the development of N-methyl-N'-nitrosoguanidine (MNNG) induced gastric cancer though levels of adduct were same as in the resistant BUF strain (Sugimura et al 1995). Susceptible to the induction of tumours of the large intestine and forestomach by 1-hydroxyanthraquinone, though incidence can be reduced by the nonsteroidal anti-inflamatory drug indomethacin (Tanaka et al 1995).

High hepatic metabolism of anilene in females (2/10) (Page and Vesell 1969). Absorbs diethylstilboestrol at intermediate rate, leading to a high incidence of mammary tumours (Dunning et al 1947, see also Rothschild et al 1987). High LD₅₀ (120mg/kg) for pentobarbital sodium (1/7) (Shearer et al 1973). Long pentobarbitone sleeping time (1/10 males, 3/10 females), Vieregge et al (1987). Susceptible to the induction of gastric tumours by N-methyl-N-nitro-N- nitrosoguanidine (Ohgaki et al 1983).

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Immunology

Resistant to the development of experimental glomerulonephritis following injection of nephritogenic antigen from bovine renal basement membrane (9/10) (Naito et al, 1991). Widely used in transplantation immunology, particularly using transplantation of ACI to LEW heart and other tissues/organs (see e.g. Tchervenkov et al 1995, Levy and Alexander 1995, Buttemeyer et al 1995). Neonatal pancreatic islets derived by non-enzymic (in vitro) isolation procedures can not be transplanted across MHC barriers without any immune suppression like most other strains but in contrast with F344 (Ketchum et al, 1992).

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Reproduction

Poor reproductive performance (9/12) and low litter size (11/12) (Hansen et al 1973). High (11%) early prenatal mortality (2/8) and high (10%) incidence of congenital malformations (Shoji 1977). High in-utero embryo mortality, which depends on maternal genotype (Cramer and Gill 1975).

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Miscellaneous

Will grow transplantable Morris hepatomas 3924A which can be used as a model for the treatment of liver cancer (Yang et al 1995).

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Buttemeyer R., Rao U., and Jones N. F. (1995) Peripheral-nerve allograft transplantation with FK506 - functional, histological, and immunological results before and after discontinuation of immunosuppression. Annals of Plastic Surgery 35, 396-401.

Cramer D. V. and Gill T. J. III (1975) Genetics of urogenital abnormalities in ACI inbred rats. Teratology 12, 27-32.

Dunning W. F., Curtis M. R., and Segaloff A. (1947) Strain differences in response to diethylstilbestrol and the induction of mammary gland and bladder cancer in the rat. Cancer Res. 7, 511-521.

Esber H. J., Menninger F. F. Jr., and Bogden A. E. (1974) Variation in serum hormone concentrations in different rat strains. Proc. Soc. Exp. Biol. Med. 146, 1050-1053.

Hansen C. T., Judge F. J., and Whitney R. A. (1973) Catalogue of NIH Rodents. DREW Publ. No. 74-606. Department of Health, Education, and Welfare, Washington, D.C.: U.S.

Harrington G. M. (1971a) Strain differences among rats initiating exploration of differing environments. Psychon. Sci. 23, 348-349.

Hirono I., Ogino H., Fujimoto M., Yamada K., Yoshida Y., Ikagawa M., and Okumura M. (1987) Induction of tumors in ACI rats given a diet containing ptaquiloside, a bracken carcinogen. J. Natl. Cancer Inst. 79, 1143-1149.

Hosaka S., Nagayama H., and Hirono I. (1984) Suppressive effect of caffeine on the development of hepatic-tumors induced by 2-acetylsminofluorene in ACI rats. Gann 75, 1058-1061.

Inoue M., Peeters B. W. M. M., van Luijtelaar E. L. J. M., Vossen J. M. H., and Coenen A. M. L. (1990) Spontaneous occurrence of spike-wave discharges in five inbred strains of rats. Physiol. Behav. 48, 199-201.

Isaacs J. T. (1984) The aging ACI/Seg versus Copenhagen male rat as a model system for the study of prostatic carcinogenesis. Cancer Res. 44, 5785-5796.

Kasai N., Kamimura A., Miyoshi I., and Ariga T. (1993) Ganglioside distribution in the liver of inbred strains of rats and the cancerous liver of LEC rats. Journal of Biochemistry 113, 251-257.

Ketchum R. J., Moore W. V., and Hegre O. D. (1992) Increased islet allograft survival after extended culture by a mechanism other than depletion of donor apcs - lack of correlation between the elimination of donor MHC class-II-positive accessory cells and increased transplantability. Transplant. 54, 347-351.

Kondo Y., Homma Y., Aso Y., and Kakizoe T. (1994) Promotional effect of 2-generation exposure to a high-fat diet on prostate carcinogenesis in ACI/Seg rats. Cancer Res. 54, 6129-6132.

Kunstyr I., Naumann S., and Werner J. (1982) Urolithiasis in female inbred SPF rats. Possible predisposition of DA and ACI strains. Z. Versuchstierk. 24, 214-218.

Levy A. E. and Alexander J. W. (1995) Administration of intragraft interleukin-4 prolongs cardiac allograft survival in rats treated with donor-specific transfusion/cyclosporine. Transplant. 60, 405-406.

Maekawa A. and Odashima S. (1975) Spontaneous tumours in ACI/N rats. J. Natl. Cancer Inst. 55, 1437-1445.

Miranda M., Bartoli G., Ragnelli A. M., Cittadini A., Palozza P., Aimola P., Zarivi O., and Bonfigli A. (1992) Copper deficiency and pigmentation in the rat - morphofunctional aspects. Journal of Submicroscopic Cytology and Pathology 24, 273-279.

Naito I., Kagawa M., Sado Y., and Okigaki T. (1991) Strain specific responses of inbred rats on the severity of experimental autoimmune glomerulonephritis - presence of a broad- spectrum of the susceptibility. International Journal of Immunopathology and Pharmacology 4, 145-154.

Ohgaki H., Kawachi T., Matsukura N., Morino K., Miyamoto M., and Sugimura T. (1983) Genetic cvontrol of susceptibility of rats to gastric carcinoma. Cancer Res. 43, 3663-3667.

Page J. G. and Vesell E. S. (1969) Hepatic drug metabolism in ten strains of Norway rat before and after pretreatment with phenobarbital. Proc. Soc. Exp. Biol. Med. 131, 256-261.

Rothschild T. C., Boylan E. S., Calhoon R. E., and Vonderharr B. K. (1987) Trans-placental effects of diethylstilbestrol on mammary development and tumorigenesis in female ACI rats. Cancer Res. 47, 4508-4516.

Scolnik M. D., Servadio C., and Abramovici A. (1994) Comparative-study of experimentally-induced benign and atypical hyperplasia in the ventral prostate of different rat strains. J. Androl. 15, 287-297.

Shain S. A., McCullough B., and Segaloff A. (1975) Spontaneous adenocarcinomas of the ventral prostate of aged A x C rats. J. Natl. Cancer Inst. 55, 177-180.

Shearer D., Creel D., and Wilson C. E. (1973) Strain differences in the response of rats to repeated injections of pentobarbital sodium. Lab. Animal Sci. 23, 662-664.

Shibutani M., Maekawa A., Okeda R., Mitsumori K., Imazawa T., Yoshida J., Onodera H., and Hayashi Y. (1993) An experimental-model for anaplastic astrocytomas and glioblastomas using adult F344 rats and N-methyl-N-nitrosourea. Acta Pathologica Japonica 43, 464-474.

Shoji R. (1977) Spontaneous occurrence of congenital malformations and mortality in prenatal inbred rats. Proc. Jpn. Acad. 53, 54-67.

Siebert U. and Wollnik F. (1991) Wheel-running activity rhythms in 2 inbred strains of laboratory rats under different photoperiods. Physiol. Behav. 50, 1137-1143.

Sugimura T., Inoue R., Ohgaki H., Ushijima T., Canzian F., and Nagao M. (1995) Genetic polymorphisms and susceptibility to cancer development. Pharmacogenetics 5, S161-S165.

Tanaka H., Hirose M., Hagiwara A., Imaida K., Shirai T., and Ito N. (1995) Rat strain differences in catechol carcinogenicity to the stomach. Food and Chemical Toxicology 33, 93-98.

Tanase H., Yamori Y., Hansen C. T., and Lovenberg W. (1982) Heart size in inbred strains of rats. Part 1. Genetic determination of the development of cardiovascular enlargement in rats. Hypertension 4, 864-872.

Tchervenkov J. I., Cofer B. R., Davies C., and Alexander J. W. (1995) Indefinite allograft survival induced by the combination of multiple donor-specific transfusions, cyclosporine, and an anti-T cell monoclonal-antibody in a protocol relevant to cadaveric organ-transplantation - the importance of prolonged posttransplant cyclosporine coverage. Transplant. 59, 821-824.

Teramoto K., Bowers J. L., Khettry U., Palombo J. D., and Clouse M. E. (1993) A rat fatty liver-transplant model. Transplant. 55, 737-741.

Vieregge V. T., Hackbarth H., and Bercher P. (1987) Die Pentobarbitalschlafzeit zur pharmakogenetischen Differenzierung von Ratteninzuchtstammen. Z. Versuchstierk. 29, 209-217.

Ward J. M., Reznik G., Stinson G. F., Lattuada C. P., Longfellow D. G., and Cameron T. P. (1980) Histogenesis and morphology of naturally occurring prostatic carcinoma in the ACI/Seg Hap BR rat. Lab. Invest. 43, 517-522.

Yang R., Lin Q., Rescorla F. J., and Grosfeld J. L. (1995) Experimental liver-cancer - improved response after hepatic-artery ligation and infusion of tumor-necrosis-factor-alpha and interferon-gamma. Surgery 118, 768-774.

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INBRED STRAINS OF RATS
Updated 9 Apr. 1998
Michael FW Festing
MRC Toxicology Unit, Hodgkin Building,
University of Leicester, UK