ACI

ACI/Ztm

Genotype:

Pigmentation genes: aa BB CC hh PP RR</DT> Mhc: RT1^a</DT> Erythrocyte antigens: RT2 ^b RT3 ^a</DT> Lymphocyte antigens: RT6 ^b RT7 ^a</DT>

Inbr. Gen.: At Ztm (1998), F37.

Origin: Curtis and Dunning (Du), 1926, at Columbia University

Institute for Cancer Research. To Heston in 1945 at F30, then to N in 1951

at F41 (8). Subsequent sublines from either Du or N. To Har from Du in

1964 at F60 (12).

Lifespan: Mean survival time 113 weeks for males, 108 weeks for

females (17).

Reproduction: Moderate reproductive performance. High incidence

of both early prenatal mortality (11% of implantations) and congenital

malformations (10% of living fetuses) reported by Shoji (24).

Behavioural Characteristics: Docile. Other behavioural characteristics

described by Harrington ( 9, 10, 11).

Tumours (Spontaneous): Males ­ testes 46%, adrenal 16%, pituitary

6%, skin and ear duct 6%, urinary bladder 4%. Females ­ pituitary 21%,

uterus 13%, mammary gland 11%, adrenal gland 6%, urinary bladder 5%, and

thymus and lymph nodes 4% (17). High incidence of cancer of the ventral

prostate reported in aged (over 34-month-old) ACI/Seg males (14, 21, 22,

25). Effects of retinoids on tumours of skin, prostate, and endocrine pancreas

studied by Ohshima et al. (18).

Tumours (Induced): Diethylstilbestrol administered with cholesterol

to adult rats induces a high incidence of mammary tumours (males 80%, females

85%) (5). When administered either pre- or postnatally, diethylstilbestrol

induces mammary tumours in females, and following a combination of pre-

and postnatal exposure, tumour multiplicity increases and tumour latency

decreases (20). Ptaquiloside, a carcinogen in bracken fern (Pteridium aquilinum),

induces adenomas, adenocarcinomas, and malignant fibrous histiocytomas

of the ileum and transitional cell carcinomas, keratinizing squamous cell

carcinomas, and sarcomas of the urinary bladder in females (13). Caffeine

supresses 2-acetyl-aminofluorene-induced hepatic tumours (14). Will grow

transplantable prostate carcinoma MC-961; gastric adenocarcinoma 599; glandular

stomach carcinoma #555; hepatomas 3683, 3930, 3924, H-35, 9098, 9108, 9121,

and R-1; skin appendage tumour 586; fibrosarcomas BP839, SCMCA-2, and R2572;

lymphosarcoma R-2788; and plasmoma IRS-6820 (7).

Other Characteristics: Urogenital abnormalities in 22-28% of

males and 18-20% of females. Aplasia of one kidney almost always associated

with aplasia of ipsilateral genital tract. Transmission of these defects

polygenic (3). Esterase alleles described by Womack (26). Major histocompatibility

complex (RT1) widely studied (e.g., 1, 2, 6, 15, 16, 27). Alphafetoprotein

and albumin genes studied by Boulter and Sell (39) and compared to those

of BUF and F344. Hepatic metabolism of aniline higher in females than in

males (19). Median lethal dose (LD50) of pentobarbital sodium 120 mg/kg

(23). Genetic marker profile described by Bender et al. (3).

References:

1. Armerding, D., D. H. Katz, and B. Benacerraf. 1974. Immune response genes in inbred rats. I. Analysis of responder status to synthetic polypeptides and low doses of bovine serum albumin. Immunogenetics 1: 329­339.

2. Armerding, D., D. H. Katz, and B. Benacerraf. 1974. Immune response genes in inbred rats. II. Segregation studies of the GT and GA genes and their linkage to the major histocompatibility complex. Immunogenetics 1: 340­351.

3. Bender, K., P. Balogh, M.F. Bertrand, M. den Bieman, O. van Deimling, S. Eghtessadi, G.A. Gutman, H. J. Hedrich, S.V. Kluge, K. Matsumoto, D.H. Moralejo, M. Nagel, A. Portal, C.-M. Prokop, R.T. Seibert and L.F.M. van Zutphen. 1994. Genetic characterization of inbred strains of the rat (Rattus norvegicus). I. Exp. Anim. Sci. 36: 151-166.

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

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

6. Goldner-Sauve, A. J., A. Fuks, and R. D. Guttmann. 1985. Structural studies of the class-II histocompatibility antigens of the ACI rat. Can. J. Biochem. Cell Biol. 63: 1241­1249.

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

8. Hansen, C. T., S. Potkay, W. T. Watson, and R. A. Whitney, Jr. 1982. NIH Rodents: 1980 Catalogue. NIH Publ. No. 83­606, U.S. Department of Health and Human Services, Washington, D.C.

9. Harrington, G. M. 1971. Strain differences among rats initiating exploration of differing environments. Psychon. Sci. 23: 348­349.

10. Harrington, G. M. 1971. Strain differences in rotating wheel activity of the rat. Psychon. Sci. 23: 363­364.

11. Harrington, G. M. 1972. Strain differences in open-field behavior of the rat. Psychon. Sci. 27: 51­53.

12. Harrington, G. M. 1981. The Har strains of rats: Origins and characteristics. Behav. Genet. 11: 445­468.

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

14. 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: 5785­5796.

15. Kunz, H. W., T. J. Gill III, and B. Borland. 1974. The genetic linkage of the immune response of poly(Glu52Lys33Tyr15) to the major histocompatibility locus in inbred rats. J. Immunogenet. 1: 277­287.

16. Luderer, A. A., P. H. Maurer, and R. T. Woodland. 1976. Genetic control of the immune response in rats to the known sequential polypeptide (Tyr-Glu-Ala-Gly)n. I. Antibody responses. J. Immunol. 117: 1079­1084.

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

18. Ohshima, M., J. M. Ward, and M. L. Wenk. 1985. Preventive and enhancing effects of retinoids on the development of naturally-occurring tumors of skin, prostate-gland, and endocrine pancreas in aged male ACI/SegHapBR rats. J. Natl. Cancer Inst. 74: 517­524.

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

20. Rothschild, T. C., E. S. Boylan, R. E. Calhoon, and B. K. Vonderharr. 1987. Transplacental effects of diethylstilbestrol on mammary development and tumorigenesis in female ACI rats. Cancer Res. 47: 4508­4516.

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

22. Shain, S. A., B. McCullough, and W. N. Nitchuck. 1979. Primary and transplantable adenocarcinomas of the AXC rat ventral prostate gland; morphologic characterization and examination of the C19-steroid metabolism of early passage tumors. J. Natl. Cancer Inst. 62: 313­322.

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

24. Shoji, R. 1977. Spontaneous occurrence of congenital malformations and mortality in prenatal inbred rats. Proc. Japan Acad. 53: 54­67.

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

26. Womack, J. E. 1973. Biochemical genetics of rat esterases: Polymorphism, tissue expression, and linkage at four loci. Biochem. Genet. 9: 13­24.

27. Würzburg, U., H. Schütt-Gerowitt, and K. Rajewsky. 1973. Characterization of an immune response gene in rats. Eur. J. Immunol. 3: 762­766.