Table 1.

Summary of testing protocols for conventional and genetically modified mouse assays.

Assay characteristics	2-year bioassay	Trp53+/−	Tg.AC	rasH2	Xpa−/−
Mouse strain used	B6C3F1	B6.129-Trp53tm1Brd*	FVB/N-Tg.AC	CB6F1-Tg-Hras2	B6.129-Xpatm1Hvs
Primary genetic background	C3HeN and C57B/6N	C57BL/6NTac	FVB/N	BALB/cByJJic and C57BL/6J	C57BL/6J
Key reference	Huff, 1999	Donehower et al., 1992	Leder et al., 1990	Saitoh et al., 1990	van Kreijl et al., 2001; van Steeg et al., 2001
Zygosity	Heterozygous	Heterozygous	Hemizygous for a mutant v-Hras1 transgene	Hemizygous for human HRAS transgene	Homozygous
Age (at start of the expt.)	6 weeks	6–8 weeks	7–9 weeks	7–9 weeks	6–8 weeks
No. male or female mice/dose	50–60	15–20	15–20	20–25	15
No. mice/cage	10	5	1	5	1(male)/>1 (female)
Treatment duration	24 months	26 or 36 weeks	26 or 36 weeks	≤26 weeks	39 weeks
Holding time	–	2 weeks	6 weeks	–	–
Route of exposure	Feed, gavage, inhalation, skin, drinking water, i.p.	Topical, diet, gavage	Topical or gavage	Gavage, diet, i.p., or water	Topical or gavage
Basis for dose selection	Maximum Tolerated Dose (MTD)	MTD from previous cancer bioassay or range finding	MTD from previous cancer bioassay	2-year bioassay	4 week dose range finding study with genetically modified mice
Number of tissues for necropsy	30–40 tissues	40 (nongenotoxic) and 12 (genotoxic)	12 tissues	40 tissues	40 tissues
Common spontaneous tumors	Hepatocellular adenomas/carcinomas, malignant lymphomas/leukemias	Lymphomas, osteosarcomas, hemangio-sarcomas	Odontogenic tumors, forestomach and skin papillomas, lung adenomas	Hemangiosarcomas, lung adenocarcinomas, skin papillomas, Harderian gland adenocarcinomas and lymphomas.	Lymphomas, lung adenomas, adrenal tumors
Predominant chemicals tested	Wide range of agents	Genotoxic	Genotoxic & nongenotoxic; tumor promoters	Genotoxic & nongenotoxic	Genotoxic carcinogens; carcinogens in general

^*The B6.129 denotes insertion of a 129 ESC gene sequence into a B6 embryo creating a congenic mouse.