The incidence of lung and spleen tumors in positive control group of Tg.rasH2 mice sourced from CLEA, Japan

The 6-month carcinogenicity study in Tg.rasH2 mice is a valid alternative to traditional 2-year bioassays in mice. Currently these mice are available from two breeder sources, viz.
Taconic, USA and CLEA, Japan.

For mice sourced from CLEA, there is a dearth of published data onpositive control urethane.

Urethane, at 1000 mg/kg bwt has been unduly toxic to mice, 1,2 but not at 500 mg/kg .

We conducted a study in Tg.rasH2 mice sourced from CLEA, Japan, to generate positive control data for urethane administered at a lower dose of 500 mg/kg bwt
on days 1, 3 and 5

• in 10 male & 10 female mice
• intraperitoneal injections,
• sacrificed at 13 weeks aer the

Observations:

• Gross necropsy.
• Lungs and spleen examined microscopically, and the tumors identified

Comparison with Published Data

Made with published¹² tumor incidence in lungs and spleen, from 60 mice, sourced from Taconic and treated with urethane at 500 mg/kg bwt on days 1, 3 & 5.

No remarkable toxicity observed at 500 mg/kg of urethane injected IP.

Tumor Incidence:

Lungs – Alveolar bronchiolar adenomas/adenocarcinomas in
all the 20/20 mice (100% incidence) (Fig. 1 & 3);
Hemangiosarcomas co-existing in 3/20 mice

Spleen – Hemangiosarcomas in all the 20/20 mice (100% incidence) (Fig. 2 & 4)

The comparison with published data in Taconic sourced Tg.rasH2 mice reveals that,

• Pulmonary adenomas/adenocarcinomas – incidence was fully comparable
• Splenic hemangiosarcomas – incidence was slightly higher despite a lower dose of urethane.
• There were no overt clinical signs of toxicity due to the lowered dose of urethane